Amino acid levels determine metabolism and CYP450 function of hepatocytes and hepatoma cell lines View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2020-03-13

AUTHORS

Ruben Boon, Manoj Kumar, Tine Tricot, Ilaria Elia, Laura Ordovas, Frank Jacobs, Jennifer One, Jonathan De Smedt, Guy Eelen, Matthew Bird, Philip Roelandt, Ginevra Doglioni, Kim Vriens, Matteo Rossi, Marta Aguirre Vazquez, Thomas Vanwelden, François Chesnais, Adil El Taghdouini, Mustapha Najimi, Etienne Sokal, David Cassiman, Jan Snoeys, Mario Monshouwer, Wei-Shou Hu, Christian Lange, Peter Carmeliet, Sarah-Maria Fendt, Catherine M. Verfaillie

ABSTRACT

Predicting drug-induced liver injury in a preclinical setting remains challenging, as cultured primary human hepatocytes (PHHs), pluripotent stem cell-derived hepatocyte-like cells (HLCs), and hepatoma cells exhibit poor drug biotransformation capacity. We here demonstrate that hepatic functionality depends more on cellular metabolism and extracellular nutrients than on developmental regulators. Specifically, we demonstrate that increasing extracellular amino acids beyond the nutritional need of HLCs and HepG2 cells induces glucose independence, mitochondrial function, and the acquisition of a transcriptional profile that is closer to PHHs. Moreover, we show that these high levels of amino acids are sufficient to drive HLC and HepG2 drug biotransformation and liver-toxin sensitivity to levels similar to those in PHHs. In conclusion, we provide data indicating that extracellular nutrient levels represent a major determinant of cellular maturity and can be utilized to guide stem cell differentiation to the hepatic lineage. More... »

PAGES

1393

References to SciGraph publications

  • 2014-01-09. Clinical development success rates for investigational drugs in NATURE BIOTECHNOLOGY
  • 2016-06-25. A multicenter assessment of single-cell models aligned to standard measures of cell health for prediction of acute hepatotoxicity in ARCHIVES OF TOXICOLOGY
  • 2013-07-03. Vascularized and functional human liver from an iPSC-derived organ bud transplant in NATURE
  • 2012-09-16. Long-Term Culture and Coculture of Primary Rat and Human Hepatocytes in EPITHELIAL CELL CULTURE PROTOCOLS
  • 2019-11-11. Autophagic lipid metabolism sustains mTORC1 activity in TSC-deficient neural stem cells in NATURE METABOLISM
  • 2013-03-09. Directed Differentiation of Pluripotent Stem Cells to Functional Hepatocytes in PLURIPOTENT STEM CELLS
  • 2012-10-16. Promotion of the efficient metabolic maturation of human pluripotent stem cell-derived hepatocytes by correcting specification defects in CELL RESEARCH
  • 2019-07-08. Glutamine independence is a selectable feature of pluripotent stem cells in NATURE METABOLISM
  • 2015-11-23. Glutamine Synthetase activity fuels nucleotide biosynthesis and supports growth of glutamine-restricted glioblastoma in NATURE CELL BIOLOGY
  • 2019-10-14. Hepatic Rab24 controls blood glucose homeostasis via improving mitochondrial plasticity in NATURE METABOLISM
  • 2003-01-06. The orphan nuclear receptor HNF4α determines PXR- and CAR-mediated xenobiotic induction of CYP3A4 in NATURE MEDICINE
  • 1995-12. The effect of amino acid composition of serum-free medium on DNA synthesis in primary hepatocyte cultures in the presence of epidermal growth factor in IN VITRO CELLULAR & DEVELOPMENTAL BIOLOGY - ANIMAL
  • 2008-12-29. WGCNA: an R package for weighted correlation network analysis in BMC BIOINFORMATICS
  • 2016-05-04. Characterization of primary human hepatocyte spheroids as a model system for drug-induced liver injury, liver function and disease in SCIENTIFIC REPORTS
  • 2005-09-19. Regulation of the small GTPase Rheb by amino acids in ONCOGENE
  • 2016-06-23. Gene network activity in cultivated primary hepatocytes is highly similar to diseased mammalian liver tissue in ARCHIVES OF TOXICOLOGY
  • 2020-02-07. Lisa: inferring transcriptional regulators through integrative modeling of public chromatin accessibility and ChIP-seq data in GENOME BIOLOGY
  • 2017-05-11. Proline metabolism supports metastasis formation and could be inhibited to selectively target metastasizing cancer cells in NATURE COMMUNICATIONS
  • 2015-11-19. Micropatterned coculture of primary human hepatocytes and supportive cells for the study of hepatotropic pathogens in NATURE PROTOCOLS
  • 2019-04-08. KLF15 regulates endobiotic and xenobiotic metabolism in NATURE METABOLISM
  • 2007-11. mTOR controls mitochondrial oxidative function through a YY1–PGC-1α transcriptional complex in NATURE
  • 2015-10-26. Long-term culture and expansion of primary human hepatocytes in NATURE BIOTECHNOLOGY
  • 2016-05-19. Interstitial Fluid Sphingosine-1-Phosphate in Murine Mammary Gland and Cancer and Human Breast Tissue and Cancer Determined by Novel Methods in JOURNAL OF MAMMARY GLAND BIOLOGY AND NEOPLASIA
  • 2007-11-18. Microscale culture of human liver cells for drug development in NATURE BIOTECHNOLOGY
  • 2018-04-05. Metabolomics activity screening for identifying metabolites that modulate phenotype in NATURE BIOTECHNOLOGY
  • 2011-02-17. Stable isotope resolved metabolomics of primary human hepatocytes reveals a stressed phenotype in METABOLOMICS
  • 2010-05-02. Metabolic oxidation regulates embryonic stem cell differentiation in NATURE CHEMICAL BIOLOGY
  • 2017-01-31. A transcriptomic study suggesting human iPSC-derived hepatocytes potentially offer a better in vitro model of hepatotoxicity than most hepatoma cell lines in CELL BIOLOGY AND TOXICOLOGY
  • Journal

    TITLE

    Nature Communications

    ISSUE

    1

    VOLUME

    11

    Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/s41467-020-15058-6

    DOI

    http://dx.doi.org/10.1038/s41467-020-15058-6

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1125612547

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/32170132


    Indexing Status Check whether this publication has been indexed by Scopus and Web Of Science using the SN Indexing Status Tool
    Incoming Citations Browse incoming citations for this publication using opencitations.net

    JSON-LD is the canonical representation for SciGraph data.

    TIP: You can open this SciGraph record using an external JSON-LD service: JSON-LD Playground Google SDTT

    [
      {
        "@context": "https://springernature.github.io/scigraph/jsonld/sgcontext.json", 
        "about": [
          {
            "id": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/06", 
            "inDefinedTermSet": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/", 
            "name": "Biological Sciences", 
            "type": "DefinedTerm"
          }, 
          {
            "id": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/0601", 
            "inDefinedTermSet": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/", 
            "name": "Biochemistry and Cell Biology", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Amino Acids", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Carcinoma, Hepatocellular", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Cell Differentiation", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Cell Line, Tumor", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Cytochrome P-450 CYP3A", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Cytochrome P-450 Enzyme System", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Female", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Gene Knockout Techniques", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Hep G2 Cells", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Hepatocyte Nuclear Factor 1-alpha", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Hepatocyte Nuclear Factor 3-gamma", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Hepatocytes", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "High-Throughput Screening Assays", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Homeodomain Proteins", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Humans", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Liver", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Liver Neoplasms", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Male", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Metabolic Engineering", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Metabolic Networks and Pathways", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Middle Aged", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Pluripotent Stem Cells", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Stem Cells", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Transcriptome", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Tumor Suppressor Proteins", 
            "type": "DefinedTerm"
          }
        ], 
        "author": [
          {
            "affiliation": {
              "alternateName": "Department of Development and Regeneration, Stem Cell Institute, KU Leuven, Leuven, Belgium", 
              "id": "http://www.grid.ac/institutes/grid.5596.f", 
              "name": [
                "Department of Development and Regeneration, Stem Cell Institute, KU Leuven, Leuven, Belgium"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Boon", 
            "givenName": "Ruben", 
            "id": "sg:person.0671747777.23", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0671747777.23"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Department of Development and Regeneration, Stem Cell Institute, KU Leuven, Leuven, Belgium", 
              "id": "http://www.grid.ac/institutes/grid.5596.f", 
              "name": [
                "Department of Development and Regeneration, Stem Cell Institute, KU Leuven, Leuven, Belgium"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Kumar", 
            "givenName": "Manoj", 
            "id": "sg:person.01360212631.05", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01360212631.05"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Department of Development and Regeneration, Stem Cell Institute, KU Leuven, Leuven, Belgium", 
              "id": "http://www.grid.ac/institutes/grid.5596.f", 
              "name": [
                "Department of Development and Regeneration, Stem Cell Institute, KU Leuven, Leuven, Belgium"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Tricot", 
            "givenName": "Tine", 
            "id": "sg:person.016136204453.32", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.016136204453.32"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Laboratory of Cellular Metabolism and Metabolic Regulation, Department of Oncology, KU Leuven and Leuven Cancer Institute (LKI), Leuven, Belgium", 
              "id": "http://www.grid.ac/institutes/grid.5596.f", 
              "name": [
                "Laboratory of Cellular Metabolism and Metabolic Regulation, VIB Center for Cancer Biology, VIB, Leuven, Belgium", 
                "Laboratory of Cellular Metabolism and Metabolic Regulation, Department of Oncology, KU Leuven and Leuven Cancer Institute (LKI), Leuven, Belgium"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Elia", 
            "givenName": "Ilaria", 
            "id": "sg:person.0707254600.80", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0707254600.80"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Present Address: Biomedical Signal Interpretation and Computational Simulation (BSICoS) Group, Arag\u00f3n Institute of Engineering Research, IIS Arag\u00f3n University of Zaragoza, Aragon I + D Foundation (ARAID), Zaragoza, Spain", 
              "id": "http://www.grid.ac/institutes/grid.11205.37", 
              "name": [
                "Department of Development and Regeneration, Stem Cell Institute, KU Leuven, Leuven, Belgium", 
                "Present Address: Biomedical Signal Interpretation and Computational Simulation (BSICoS) Group, Arag\u00f3n Institute of Engineering Research, IIS Arag\u00f3n University of Zaragoza, Aragon I + D Foundation (ARAID), Zaragoza, Spain"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Ordovas", 
            "givenName": "Laura", 
            "id": "sg:person.01114443415.72", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01114443415.72"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Janssen Research and Development, Beerse, Belgium", 
              "id": "http://www.grid.ac/institutes/grid.419619.2", 
              "name": [
                "Janssen Research and Development, Beerse, Belgium"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Jacobs", 
            "givenName": "Frank", 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Stem Cell Institute, University of Minnesota, Minneapolis, MN USA", 
              "id": "http://www.grid.ac/institutes/grid.17635.36", 
              "name": [
                "Department of Chemical Engineering and Materials Science, University of Minnesota, Minneapolis, MN USA", 
                "Stem Cell Institute, University of Minnesota, Minneapolis, MN USA"
              ], 
              "type": "Organization"
            }, 
            "familyName": "One", 
            "givenName": "Jennifer", 
            "id": "sg:person.013605134364.50", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.013605134364.50"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Department of Development and Regeneration, Stem Cell Institute, KU Leuven, Leuven, Belgium", 
              "id": "http://www.grid.ac/institutes/grid.5596.f", 
              "name": [
                "Department of Development and Regeneration, Stem Cell Institute, KU Leuven, Leuven, Belgium"
              ], 
              "type": "Organization"
            }, 
            "familyName": "De Smedt", 
            "givenName": "Jonathan", 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Laboratory of Angiogenesis and Vascular Metabolism, Center of Cancer Biology, VIB, Leuven, Belgium", 
              "id": "http://www.grid.ac/institutes/grid.11486.3a", 
              "name": [
                "Laboratory of Angiogenesis and Vascular Metabolism, Department of Oncology, KU Leuven, Leuven, Belgium", 
                "Laboratory of Angiogenesis and Vascular Metabolism, Center of Cancer Biology, VIB, Leuven, Belgium"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Eelen", 
            "givenName": "Guy", 
            "id": "sg:person.01313265732.75", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01313265732.75"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Hepatology, Department of Clinical and Experimental Medicine, KU Leuven, Leuven, Belgium", 
              "id": "http://www.grid.ac/institutes/grid.5596.f", 
              "name": [
                "Hepatology, Department of Clinical and Experimental Medicine, KU Leuven, Leuven, Belgium"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Bird", 
            "givenName": "Matthew", 
            "id": "sg:person.0704536050.07", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0704536050.07"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Present Address: Department of Gastroenterology and Hepatology, UZ Leuven, Leuven, Belgium", 
              "id": "http://www.grid.ac/institutes/grid.410569.f", 
              "name": [
                "Department of Development and Regeneration, Stem Cell Institute, KU Leuven, Leuven, Belgium", 
                "Hepatology, Department of Clinical and Experimental Medicine, KU Leuven, Leuven, Belgium", 
                "Present Address: Translational Research in GastroIntestinal Disorders (TARGID), Department of Chronic Diseases, Metabolism and Ageing (CHROMETA), KU Leuven, Leuven, Belgium", 
                "Present Address: Department of Gastroenterology and Hepatology, UZ Leuven, Leuven, Belgium"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Roelandt", 
            "givenName": "Philip", 
            "id": "sg:person.01327773553.26", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01327773553.26"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Laboratory of Cellular Metabolism and Metabolic Regulation, Department of Oncology, KU Leuven and Leuven Cancer Institute (LKI), Leuven, Belgium", 
              "id": "http://www.grid.ac/institutes/grid.5596.f", 
              "name": [
                "Laboratory of Cellular Metabolism and Metabolic Regulation, VIB Center for Cancer Biology, VIB, Leuven, Belgium", 
                "Laboratory of Cellular Metabolism and Metabolic Regulation, Department of Oncology, KU Leuven and Leuven Cancer Institute (LKI), Leuven, Belgium"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Doglioni", 
            "givenName": "Ginevra", 
            "id": "sg:person.016361550722.19", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.016361550722.19"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Laboratory of Cellular Metabolism and Metabolic Regulation, Department of Oncology, KU Leuven and Leuven Cancer Institute (LKI), Leuven, Belgium", 
              "id": "http://www.grid.ac/institutes/grid.5596.f", 
              "name": [
                "Laboratory of Cellular Metabolism and Metabolic Regulation, VIB Center for Cancer Biology, VIB, Leuven, Belgium", 
                "Laboratory of Cellular Metabolism and Metabolic Regulation, Department of Oncology, KU Leuven and Leuven Cancer Institute (LKI), Leuven, Belgium"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Vriens", 
            "givenName": "Kim", 
            "id": "sg:person.0654416175.72", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0654416175.72"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Laboratory of Cellular Metabolism and Metabolic Regulation, Department of Oncology, KU Leuven and Leuven Cancer Institute (LKI), Leuven, Belgium", 
              "id": "http://www.grid.ac/institutes/grid.5596.f", 
              "name": [
                "Laboratory of Cellular Metabolism and Metabolic Regulation, VIB Center for Cancer Biology, VIB, Leuven, Belgium", 
                "Laboratory of Cellular Metabolism and Metabolic Regulation, Department of Oncology, KU Leuven and Leuven Cancer Institute (LKI), Leuven, Belgium"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Rossi", 
            "givenName": "Matteo", 
            "id": "sg:person.011220302613.48", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.011220302613.48"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Department of Development and Regeneration, Stem Cell Institute, KU Leuven, Leuven, Belgium", 
              "id": "http://www.grid.ac/institutes/grid.5596.f", 
              "name": [
                "Department of Development and Regeneration, Stem Cell Institute, KU Leuven, Leuven, Belgium"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Vazquez", 
            "givenName": "Marta Aguirre", 
            "id": "sg:person.015345704751.25", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.015345704751.25"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Department of Development and Regeneration, Stem Cell Institute, KU Leuven, Leuven, Belgium", 
              "id": "http://www.grid.ac/institutes/grid.5596.f", 
              "name": [
                "Department of Development and Regeneration, Stem Cell Institute, KU Leuven, Leuven, Belgium"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Vanwelden", 
            "givenName": "Thomas", 
            "id": "sg:person.01244040671.91", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01244040671.91"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Department of Development and Regeneration, Stem Cell Institute, KU Leuven, Leuven, Belgium", 
              "id": "http://www.grid.ac/institutes/grid.5596.f", 
              "name": [
                "Department of Development and Regeneration, Stem Cell Institute, KU Leuven, Leuven, Belgium"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Chesnais", 
            "givenName": "Fran\u00e7ois", 
            "id": "sg:person.016273370760.93", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.016273370760.93"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Laboratory of Pediatric Hepatology and Cell Therapy, Universit Catholique de Louvain & Cliniques Universitaires St Luc, Institut de Recherche Clinique et Exp\u00e9rimentale (IREC), Brussels, Belgium", 
              "id": "http://www.grid.ac/institutes/grid.7942.8", 
              "name": [
                "Laboratory of Pediatric Hepatology and Cell Therapy, Universit Catholique de Louvain & Cliniques Universitaires St Luc, Institut de Recherche Clinique et Exp\u00e9rimentale (IREC), Brussels, Belgium"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Taghdouini", 
            "givenName": "Adil El", 
            "id": "sg:person.016174635653.11", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.016174635653.11"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Laboratory of Pediatric Hepatology and Cell Therapy, Universit Catholique de Louvain & Cliniques Universitaires St Luc, Institut de Recherche Clinique et Exp\u00e9rimentale (IREC), Brussels, Belgium", 
              "id": "http://www.grid.ac/institutes/grid.7942.8", 
              "name": [
                "Laboratory of Pediatric Hepatology and Cell Therapy, Universit Catholique de Louvain & Cliniques Universitaires St Luc, Institut de Recherche Clinique et Exp\u00e9rimentale (IREC), Brussels, Belgium"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Najimi", 
            "givenName": "Mustapha", 
            "id": "sg:person.01267404401.45", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01267404401.45"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Laboratory of Pediatric Hepatology and Cell Therapy, Universit Catholique de Louvain & Cliniques Universitaires St Luc, Institut de Recherche Clinique et Exp\u00e9rimentale (IREC), Brussels, Belgium", 
              "id": "http://www.grid.ac/institutes/grid.7942.8", 
              "name": [
                "Laboratory of Pediatric Hepatology and Cell Therapy, Universit Catholique de Louvain & Cliniques Universitaires St Luc, Institut de Recherche Clinique et Exp\u00e9rimentale (IREC), Brussels, Belgium"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Sokal", 
            "givenName": "Etienne", 
            "id": "sg:person.01305305435.04", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01305305435.04"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Hepatology, Department of Clinical and Experimental Medicine, KU Leuven, Leuven, Belgium", 
              "id": "http://www.grid.ac/institutes/grid.5596.f", 
              "name": [
                "Hepatology, Department of Clinical and Experimental Medicine, KU Leuven, Leuven, Belgium"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Cassiman", 
            "givenName": "David", 
            "id": "sg:person.01054163573.07", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01054163573.07"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Stem Cell Institute, University of Minnesota, Minneapolis, MN USA", 
              "id": "http://www.grid.ac/institutes/grid.17635.36", 
              "name": [
                "Department of Chemical Engineering and Materials Science, University of Minnesota, Minneapolis, MN USA", 
                "Stem Cell Institute, University of Minnesota, Minneapolis, MN USA"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Snoeys", 
            "givenName": "Jan", 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Stem Cell Institute, University of Minnesota, Minneapolis, MN USA", 
              "id": "http://www.grid.ac/institutes/grid.17635.36", 
              "name": [
                "Department of Chemical Engineering and Materials Science, University of Minnesota, Minneapolis, MN USA", 
                "Stem Cell Institute, University of Minnesota, Minneapolis, MN USA"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Monshouwer", 
            "givenName": "Mario", 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Stem Cell Institute, University of Minnesota, Minneapolis, MN USA", 
              "id": "http://www.grid.ac/institutes/grid.17635.36", 
              "name": [
                "Department of Chemical Engineering and Materials Science, University of Minnesota, Minneapolis, MN USA", 
                "Stem Cell Institute, University of Minnesota, Minneapolis, MN USA"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Hu", 
            "givenName": "Wei-Shou", 
            "id": "sg:person.01064261433.49", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01064261433.49"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Laboratory of Angiogenesis and Vascular Metabolism, Center of Cancer Biology, VIB, Leuven, Belgium", 
              "id": "http://www.grid.ac/institutes/grid.11486.3a", 
              "name": [
                "Laboratory of Angiogenesis and Vascular Metabolism, Department of Oncology, KU Leuven, Leuven, Belgium", 
                "Laboratory of Angiogenesis and Vascular Metabolism, Center of Cancer Biology, VIB, Leuven, Belgium"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Lange", 
            "givenName": "Christian", 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Laboratory of Angiogenesis and Vascular Metabolism, Center of Cancer Biology, VIB, Leuven, Belgium", 
              "id": "http://www.grid.ac/institutes/grid.11486.3a", 
              "name": [
                "Laboratory of Angiogenesis and Vascular Metabolism, Department of Oncology, KU Leuven, Leuven, Belgium", 
                "Laboratory of Angiogenesis and Vascular Metabolism, Center of Cancer Biology, VIB, Leuven, Belgium"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Carmeliet", 
            "givenName": "Peter", 
            "id": "sg:person.01033041553.19", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01033041553.19"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Laboratory of Cellular Metabolism and Metabolic Regulation, Department of Oncology, KU Leuven and Leuven Cancer Institute (LKI), Leuven, Belgium", 
              "id": "http://www.grid.ac/institutes/grid.5596.f", 
              "name": [
                "Laboratory of Cellular Metabolism and Metabolic Regulation, VIB Center for Cancer Biology, VIB, Leuven, Belgium", 
                "Laboratory of Cellular Metabolism and Metabolic Regulation, Department of Oncology, KU Leuven and Leuven Cancer Institute (LKI), Leuven, Belgium"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Fendt", 
            "givenName": "Sarah-Maria", 
            "id": "sg:person.0620030745.13", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0620030745.13"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Department of Development and Regeneration, Stem Cell Institute, KU Leuven, Leuven, Belgium", 
              "id": "http://www.grid.ac/institutes/grid.5596.f", 
              "name": [
                "Department of Development and Regeneration, Stem Cell Institute, KU Leuven, Leuven, Belgium"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Verfaillie", 
            "givenName": "Catherine M.", 
            "id": "sg:person.01037646713.05", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01037646713.05"
            ], 
            "type": "Person"
          }
        ], 
        "citation": [
          {
            "id": "sg:pub.10.1007/s10911-016-9354-7", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1011341548", 
              "https://doi.org/10.1007/s10911-016-9354-7"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/srep25187", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1028498125", 
              "https://doi.org/10.1038/srep25187"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/s42255-019-0137-5", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1122475460", 
              "https://doi.org/10.1038/s42255-019-0137-5"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1007/s11306-011-0284-5", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1051861558", 
              "https://doi.org/10.1007/s11306-011-0284-5"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1007/bf02634571", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1024847488", 
              "https://doi.org/10.1007/bf02634571"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/ncb3272", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1032287924", 
              "https://doi.org/10.1038/ncb3272"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/sj.onc.1209106", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1034184478", 
              "https://doi.org/10.1038/sj.onc.1209106"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1007/s00204-016-1745-4", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1039080201", 
              "https://doi.org/10.1007/s00204-016-1745-4"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/nchembio.364", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1020884064", 
              "https://doi.org/10.1038/nchembio.364"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1007/s10565-017-9383-z", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1083400234", 
              "https://doi.org/10.1007/s10565-017-9383-z"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/cr.2012.144", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1029165674", 
              "https://doi.org/10.1038/cr.2012.144"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1186/s13059-020-1934-6", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1124677203", 
              "https://doi.org/10.1186/s13059-020-1934-6"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/ncomms15267", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1085389814", 
              "https://doi.org/10.1038/ncomms15267"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1186/1471-2105-9-559", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1020312314", 
              "https://doi.org/10.1186/1471-2105-9-559"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/s42255-019-0082-3", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1117823480", 
              "https://doi.org/10.1038/s42255-019-0082-3"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/nbt.3377", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1033847015", 
              "https://doi.org/10.1038/nbt.3377"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1007/s00204-016-1761-4", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1013698897", 
              "https://doi.org/10.1007/s00204-016-1761-4"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1007/978-1-62703-348-0_11", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1011996516", 
              "https://doi.org/10.1007/978-1-62703-348-0_11"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/nbt.4101", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1103157300", 
              "https://doi.org/10.1038/nbt.4101"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1007/978-1-62703-125-7_17", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1005738391", 
              "https://doi.org/10.1007/978-1-62703-125-7_17"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/nbt.2786", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1013732820", 
              "https://doi.org/10.1038/nbt.2786"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/s42255-019-0124-x", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1121787070", 
              "https://doi.org/10.1038/s42255-019-0124-x"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/nm815", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1016854060", 
              "https://doi.org/10.1038/nm815"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/nbt1361", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1045539531", 
              "https://doi.org/10.1038/nbt1361"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/s42255-019-0054-7", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1113305931", 
              "https://doi.org/10.1038/s42255-019-0054-7"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/nature12271", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1034831733", 
              "https://doi.org/10.1038/nature12271"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/nprot.2015.128", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1025360205", 
              "https://doi.org/10.1038/nprot.2015.128"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/nature06322", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1010205458", 
              "https://doi.org/10.1038/nature06322"
            ], 
            "type": "CreativeWork"
          }
        ], 
        "datePublished": "2020-03-13", 
        "datePublishedReg": "2020-03-13", 
        "description": "Predicting drug-induced liver injury in a preclinical setting remains challenging, as cultured primary human hepatocytes (PHHs), pluripotent stem cell-derived hepatocyte-like cells (HLCs), and hepatoma cells exhibit poor drug biotransformation capacity. We here demonstrate that hepatic functionality depends more on cellular metabolism and extracellular nutrients than on developmental regulators. Specifically, we demonstrate that increasing extracellular amino acids beyond the nutritional need of HLCs and HepG2 cells induces glucose independence, mitochondrial function, and the acquisition of a transcriptional profile that is closer to PHHs. Moreover, we show that these high levels of amino acids are sufficient to drive HLC and HepG2 drug biotransformation and liver-toxin sensitivity to levels similar to those in PHHs. In conclusion, we provide data indicating that extracellular nutrient levels represent a major determinant of cellular maturity and can be utilized to guide stem cell differentiation to the hepatic lineage.", 
        "genre": "article", 
        "id": "sg:pub.10.1038/s41467-020-15058-6", 
        "inLanguage": "en", 
        "isAccessibleForFree": true, 
        "isFundedItemOf": [
          {
            "id": "sg:grant.8508280", 
            "type": "MonetaryGrant"
          }, 
          {
            "id": "sg:grant.8514437", 
            "type": "MonetaryGrant"
          }, 
          {
            "id": "sg:grant.4456769", 
            "type": "MonetaryGrant"
          }, 
          {
            "id": "sg:grant.3939447", 
            "type": "MonetaryGrant"
          }
        ], 
        "isPartOf": [
          {
            "id": "sg:journal.1043282", 
            "issn": [
              "2041-1723"
            ], 
            "name": "Nature Communications", 
            "publisher": "Springer Nature", 
            "type": "Periodical"
          }, 
          {
            "issueNumber": "1", 
            "type": "PublicationIssue"
          }, 
          {
            "type": "PublicationVolume", 
            "volumeNumber": "11"
          }
        ], 
        "keywords": [
          "hepatocyte-like cells", 
          "primary human hepatocytes", 
          "amino acids", 
          "extracellular nutrient levels", 
          "stem cell differentiation", 
          "extracellular amino acids", 
          "developmental regulators", 
          "stem cell-derived hepatocyte-like cells", 
          "extracellular nutrients", 
          "amino acid levels", 
          "cell-derived hepatocyte-like cells", 
          "transcriptional profiles", 
          "cellular metabolism", 
          "hepatoma cell line", 
          "cell differentiation", 
          "mitochondrial function", 
          "nutrient levels", 
          "hepatic lineage", 
          "drug-induced liver injury", 
          "cultured primary human hepatocytes", 
          "hepatoma cells", 
          "cell lines", 
          "HepG2 cells", 
          "liver injury", 
          "cellular maturity", 
          "biotransformation capacity", 
          "preclinical setting", 
          "cells", 
          "human hepatocytes", 
          "drug biotransformation", 
          "hepatic functionality", 
          "metabolism", 
          "acid levels", 
          "lineages", 
          "major determinant", 
          "nutritional needs", 
          "regulator", 
          "hepatocytes", 
          "differentiation", 
          "acid", 
          "high levels", 
          "nutrients", 
          "levels", 
          "function", 
          "injury", 
          "maturity", 
          "biotransformation", 
          "lines", 
          "conclusion", 
          "setting", 
          "determinants", 
          "sensitivity", 
          "profile", 
          "acquisition", 
          "need", 
          "capacity", 
          "data", 
          "functionality", 
          "independence", 
          "poor drug biotransformation capacity", 
          "drug biotransformation capacity", 
          "glucose independence", 
          "HepG2 drug biotransformation", 
          "liver-toxin sensitivity", 
          "CYP450 function"
        ], 
        "name": "Amino acid levels determine metabolism and CYP450 function of hepatocytes and hepatoma cell lines", 
        "pagination": "1393", 
        "productId": [
          {
            "name": "dimensions_id", 
            "type": "PropertyValue", 
            "value": [
              "pub.1125612547"
            ]
          }, 
          {
            "name": "doi", 
            "type": "PropertyValue", 
            "value": [
              "10.1038/s41467-020-15058-6"
            ]
          }, 
          {
            "name": "pubmed_id", 
            "type": "PropertyValue", 
            "value": [
              "32170132"
            ]
          }
        ], 
        "sameAs": [
          "https://doi.org/10.1038/s41467-020-15058-6", 
          "https://app.dimensions.ai/details/publication/pub.1125612547"
        ], 
        "sdDataset": "articles", 
        "sdDatePublished": "2022-01-01T18:57", 
        "sdLicense": "https://scigraph.springernature.com/explorer/license/", 
        "sdPublisher": {
          "name": "Springer Nature - SN SciGraph project", 
          "type": "Organization"
        }, 
        "sdSource": "s3://com-springernature-scigraph/baseset/20220101/entities/gbq_results/article/article_859.jsonl", 
        "type": "ScholarlyArticle", 
        "url": "https://doi.org/10.1038/s41467-020-15058-6"
      }
    ]
     

    Download the RDF metadata as:  json-ld nt turtle xml License info

    HOW TO GET THIS DATA PROGRAMMATICALLY:

    JSON-LD is a popular format for linked data which is fully compatible with JSON.

    curl -H 'Accept: application/ld+json' 'https://scigraph.springernature.com/pub.10.1038/s41467-020-15058-6'

    N-Triples is a line-based linked data format ideal for batch operations.

    curl -H 'Accept: application/n-triples' 'https://scigraph.springernature.com/pub.10.1038/s41467-020-15058-6'

    Turtle is a human-readable linked data format.

    curl -H 'Accept: text/turtle' 'https://scigraph.springernature.com/pub.10.1038/s41467-020-15058-6'

    RDF/XML is a standard XML format for linked data.

    curl -H 'Accept: application/rdf+xml' 'https://scigraph.springernature.com/pub.10.1038/s41467-020-15058-6'


     

    This table displays all metadata directly associated to this object as RDF triples.

    559 TRIPLES      22 PREDICATES      144 URIs      108 LITERALS      32 BLANK NODES

    Subject Predicate Object
    1 sg:pub.10.1038/s41467-020-15058-6 schema:about N007c1d5e521a4f66b5904d70e7670826
    2 N050b4219949a4f16855d25244fb65b11
    3 N08b5bee6eb274c68ad74ef3a1d2f5458
    4 N2501fd69a46f4633a9b497662452d5e2
    5 N270325efe35b46bc8848be2024b3ce71
    6 N2b094500fb834227ba31f7ab87bcd716
    7 N2b25a8940d634887ab1272eddfb629f6
    8 N498dd123f2b6475db2c4e6a420c73d3f
    9 N5c1ab5c3f73046f8b528d57f1c8ea46d
    10 N64120bc340ce498d8752cd479195986a
    11 N75b64da2ff484ce0a7439518270908a6
    12 N77935abfd35449ab8d68ed4ff9d2e6a2
    13 N7d349edc7f624d72a4fd147aa88aa500
    14 N7f2a967eff6a4de98f71ddaf30d730a5
    15 N802a21d0cd5e48dd887a4c99449b2c23
    16 N8f3d928aabb346d2a5c37258b0012dad
    17 N95a9c6bc73084c4bb00f9a27b0dce177
    18 Na147b6837abc46a8a9f77312178d7234
    19 Na7b28073d076404da1d0afaeb3fcb634
    20 Nac29447c23234ebf87c72f40bc207309
    21 Ncb2712017fd047e788f12bafc6faddf5
    22 Ncb67c402ca4b4d16ade0cb5496299520
    23 Nd07f6fd02bae427498857a79ffb03f9b
    24 Ndabebafcdfb146699b4a892bdfcdd9d8
    25 Nfdc31c4aff6445d3b971fa8df9780322
    26 anzsrc-for:06
    27 anzsrc-for:0601
    28 schema:author N9b368f63896145668aea3178da725139
    29 schema:citation sg:pub.10.1007/978-1-62703-125-7_17
    30 sg:pub.10.1007/978-1-62703-348-0_11
    31 sg:pub.10.1007/bf02634571
    32 sg:pub.10.1007/s00204-016-1745-4
    33 sg:pub.10.1007/s00204-016-1761-4
    34 sg:pub.10.1007/s10565-017-9383-z
    35 sg:pub.10.1007/s10911-016-9354-7
    36 sg:pub.10.1007/s11306-011-0284-5
    37 sg:pub.10.1038/cr.2012.144
    38 sg:pub.10.1038/nature06322
    39 sg:pub.10.1038/nature12271
    40 sg:pub.10.1038/nbt.2786
    41 sg:pub.10.1038/nbt.3377
    42 sg:pub.10.1038/nbt.4101
    43 sg:pub.10.1038/nbt1361
    44 sg:pub.10.1038/ncb3272
    45 sg:pub.10.1038/nchembio.364
    46 sg:pub.10.1038/ncomms15267
    47 sg:pub.10.1038/nm815
    48 sg:pub.10.1038/nprot.2015.128
    49 sg:pub.10.1038/s42255-019-0054-7
    50 sg:pub.10.1038/s42255-019-0082-3
    51 sg:pub.10.1038/s42255-019-0124-x
    52 sg:pub.10.1038/s42255-019-0137-5
    53 sg:pub.10.1038/sj.onc.1209106
    54 sg:pub.10.1038/srep25187
    55 sg:pub.10.1186/1471-2105-9-559
    56 sg:pub.10.1186/s13059-020-1934-6
    57 schema:datePublished 2020-03-13
    58 schema:datePublishedReg 2020-03-13
    59 schema:description Predicting drug-induced liver injury in a preclinical setting remains challenging, as cultured primary human hepatocytes (PHHs), pluripotent stem cell-derived hepatocyte-like cells (HLCs), and hepatoma cells exhibit poor drug biotransformation capacity. We here demonstrate that hepatic functionality depends more on cellular metabolism and extracellular nutrients than on developmental regulators. Specifically, we demonstrate that increasing extracellular amino acids beyond the nutritional need of HLCs and HepG2 cells induces glucose independence, mitochondrial function, and the acquisition of a transcriptional profile that is closer to PHHs. Moreover, we show that these high levels of amino acids are sufficient to drive HLC and HepG2 drug biotransformation and liver-toxin sensitivity to levels similar to those in PHHs. In conclusion, we provide data indicating that extracellular nutrient levels represent a major determinant of cellular maturity and can be utilized to guide stem cell differentiation to the hepatic lineage.
    60 schema:genre article
    61 schema:inLanguage en
    62 schema:isAccessibleForFree true
    63 schema:isPartOf N2b2a29af8f3f4b43bef8872bb1116f7f
    64 Nb6f3b893cfe944048aac6d7f6ad2685f
    65 sg:journal.1043282
    66 schema:keywords CYP450 function
    67 HepG2 cells
    68 HepG2 drug biotransformation
    69 acid
    70 acid levels
    71 acquisition
    72 amino acid levels
    73 amino acids
    74 biotransformation
    75 biotransformation capacity
    76 capacity
    77 cell differentiation
    78 cell lines
    79 cell-derived hepatocyte-like cells
    80 cells
    81 cellular maturity
    82 cellular metabolism
    83 conclusion
    84 cultured primary human hepatocytes
    85 data
    86 determinants
    87 developmental regulators
    88 differentiation
    89 drug biotransformation
    90 drug biotransformation capacity
    91 drug-induced liver injury
    92 extracellular amino acids
    93 extracellular nutrient levels
    94 extracellular nutrients
    95 function
    96 functionality
    97 glucose independence
    98 hepatic functionality
    99 hepatic lineage
    100 hepatocyte-like cells
    101 hepatocytes
    102 hepatoma cell line
    103 hepatoma cells
    104 high levels
    105 human hepatocytes
    106 independence
    107 injury
    108 levels
    109 lineages
    110 lines
    111 liver injury
    112 liver-toxin sensitivity
    113 major determinant
    114 maturity
    115 metabolism
    116 mitochondrial function
    117 need
    118 nutrient levels
    119 nutrients
    120 nutritional needs
    121 poor drug biotransformation capacity
    122 preclinical setting
    123 primary human hepatocytes
    124 profile
    125 regulator
    126 sensitivity
    127 setting
    128 stem cell differentiation
    129 stem cell-derived hepatocyte-like cells
    130 transcriptional profiles
    131 schema:name Amino acid levels determine metabolism and CYP450 function of hepatocytes and hepatoma cell lines
    132 schema:pagination 1393
    133 schema:productId N1327ababb4294649a9c0919dcc692d81
    134 Ncee626592311487fb76ddd9d83a88a82
    135 Ne8d83c04f5e04818a809ed0fa8ef43d6
    136 schema:sameAs https://app.dimensions.ai/details/publication/pub.1125612547
    137 https://doi.org/10.1038/s41467-020-15058-6
    138 schema:sdDatePublished 2022-01-01T18:57
    139 schema:sdLicense https://scigraph.springernature.com/explorer/license/
    140 schema:sdPublisher N13fba4af259b41799ec08cef85e29fe7
    141 schema:url https://doi.org/10.1038/s41467-020-15058-6
    142 sgo:license sg:explorer/license/
    143 sgo:sdDataset articles
    144 rdf:type schema:ScholarlyArticle
    145 N007c1d5e521a4f66b5904d70e7670826 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    146 schema:name Cytochrome P-450 CYP3A
    147 rdf:type schema:DefinedTerm
    148 N0097de26a75141dc8fed08afbba1c028 rdf:first sg:person.0704536050.07
    149 rdf:rest Nb1ccf1d40fb44d1f96fe83aef46993f1
    150 N050b4219949a4f16855d25244fb65b11 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    151 schema:name Liver
    152 rdf:type schema:DefinedTerm
    153 N058daa7550264e2895bfafa27cd5f86a rdf:first sg:person.01305305435.04
    154 rdf:rest N0aca206529fa4ed9b2d90c63219466d8
    155 N08b5bee6eb274c68ad74ef3a1d2f5458 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    156 schema:name Amino Acids
    157 rdf:type schema:DefinedTerm
    158 N0aca206529fa4ed9b2d90c63219466d8 rdf:first sg:person.01054163573.07
    159 rdf:rest Nf5020415bedd4ff481192879af5aa502
    160 N10905aba6a414333b30309bea93332e9 rdf:first sg:person.013605134364.50
    161 rdf:rest Nc1a2f907ba6949599f91629fd030610d
    162 N1327ababb4294649a9c0919dcc692d81 schema:name dimensions_id
    163 schema:value pub.1125612547
    164 rdf:type schema:PropertyValue
    165 N13fba4af259b41799ec08cef85e29fe7 schema:name Springer Nature - SN SciGraph project
    166 rdf:type schema:Organization
    167 N193653d1a2cf457b83406bd1b51921c2 rdf:first N306f284bb09b424cbf79ce512ba5ed89
    168 rdf:rest N77fd78123fd84001a18bf5de5356e9a1
    169 N19e4af6e9d9149ad8007e47ae4ebdae5 rdf:first sg:person.01114443415.72
    170 rdf:rest Nb246f459b3974e81b89bc5bff9406391
    171 N1a631b49af304bf58b7886c61bf84228 rdf:first sg:person.0620030745.13
    172 rdf:rest N9ace50a9323a4e3599e912e059380a00
    173 N2501fd69a46f4633a9b497662452d5e2 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    174 schema:name Cytochrome P-450 Enzyme System
    175 rdf:type schema:DefinedTerm
    176 N270325efe35b46bc8848be2024b3ce71 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    177 schema:name Hep G2 Cells
    178 rdf:type schema:DefinedTerm
    179 N2a7ba16378124432aa4c14658867fcaf rdf:first sg:person.016174635653.11
    180 rdf:rest Ne83987768b924b14a0200ebd3d4d8c74
    181 N2b094500fb834227ba31f7ab87bcd716 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    182 schema:name Female
    183 rdf:type schema:DefinedTerm
    184 N2b25a8940d634887ab1272eddfb629f6 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    185 schema:name Hepatocyte Nuclear Factor 1-alpha
    186 rdf:type schema:DefinedTerm
    187 N2b2a29af8f3f4b43bef8872bb1116f7f schema:volumeNumber 11
    188 rdf:type schema:PublicationVolume
    189 N2d828ac5f97743e7a08fa728bb54ee6a schema:affiliation grid-institutes:grid.5596.f
    190 schema:familyName De Smedt
    191 schema:givenName Jonathan
    192 rdf:type schema:Person
    193 N306f284bb09b424cbf79ce512ba5ed89 schema:affiliation grid-institutes:grid.17635.36
    194 schema:familyName Monshouwer
    195 schema:givenName Mario
    196 rdf:type schema:Person
    197 N3c46d9f6a28845618541846f23f4dee7 schema:affiliation grid-institutes:grid.419619.2
    198 schema:familyName Jacobs
    199 schema:givenName Frank
    200 rdf:type schema:Person
    201 N3fe95fbaafc748d3a466717dfe65beda rdf:first N6868451e3ce442c08216e4dff0579064
    202 rdf:rest Na8f4299d86ef46ba85c39f9579d9784a
    203 N45babce50f5945c2b69b62fb5a687869 rdf:first sg:person.016273370760.93
    204 rdf:rest N2a7ba16378124432aa4c14658867fcaf
    205 N47a41ed270ac41a4a1ec0fdf665f90e2 rdf:first sg:person.01360212631.05
    206 rdf:rest N5a35c10860184f7e96e71dc0401144ec
    207 N498dd123f2b6475db2c4e6a420c73d3f schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    208 schema:name Hepatocyte Nuclear Factor 3-gamma
    209 rdf:type schema:DefinedTerm
    210 N597b6ddbbec54642a8e21312628bfaa9 rdf:first sg:person.01244040671.91
    211 rdf:rest N45babce50f5945c2b69b62fb5a687869
    212 N5a35c10860184f7e96e71dc0401144ec rdf:first sg:person.016136204453.32
    213 rdf:rest N7c2ca59421534b24a150c2bfa1519eaf
    214 N5c1ab5c3f73046f8b528d57f1c8ea46d schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    215 schema:name Metabolic Engineering
    216 rdf:type schema:DefinedTerm
    217 N64120bc340ce498d8752cd479195986a schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    218 schema:name Humans
    219 rdf:type schema:DefinedTerm
    220 N674f681fc8ec4a679e961d30a3f252e6 rdf:first sg:person.01313265732.75
    221 rdf:rest N0097de26a75141dc8fed08afbba1c028
    222 N6868451e3ce442c08216e4dff0579064 schema:affiliation grid-institutes:grid.11486.3a
    223 schema:familyName Lange
    224 schema:givenName Christian
    225 rdf:type schema:Person
    226 N75b64da2ff484ce0a7439518270908a6 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    227 schema:name Carcinoma, Hepatocellular
    228 rdf:type schema:DefinedTerm
    229 N77935abfd35449ab8d68ed4ff9d2e6a2 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    230 schema:name High-Throughput Screening Assays
    231 rdf:type schema:DefinedTerm
    232 N77fd78123fd84001a18bf5de5356e9a1 rdf:first sg:person.01064261433.49
    233 rdf:rest N3fe95fbaafc748d3a466717dfe65beda
    234 N7c2ca59421534b24a150c2bfa1519eaf rdf:first sg:person.0707254600.80
    235 rdf:rest N19e4af6e9d9149ad8007e47ae4ebdae5
    236 N7d349edc7f624d72a4fd147aa88aa500 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    237 schema:name Stem Cells
    238 rdf:type schema:DefinedTerm
    239 N7f2a967eff6a4de98f71ddaf30d730a5 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    240 schema:name Cell Differentiation
    241 rdf:type schema:DefinedTerm
    242 N802a21d0cd5e48dd887a4c99449b2c23 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    243 schema:name Middle Aged
    244 rdf:type schema:DefinedTerm
    245 N8f3ce00d2538421bb81d096df32a29bc rdf:first sg:person.0654416175.72
    246 rdf:rest Nb9247a6cb70147198a76e70983f9f724
    247 N8f3d928aabb346d2a5c37258b0012dad schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    248 schema:name Homeodomain Proteins
    249 rdf:type schema:DefinedTerm
    250 N95a9c6bc73084c4bb00f9a27b0dce177 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    251 schema:name Liver Neoplasms
    252 rdf:type schema:DefinedTerm
    253 N9ace50a9323a4e3599e912e059380a00 rdf:first sg:person.01037646713.05
    254 rdf:rest rdf:nil
    255 N9b368f63896145668aea3178da725139 rdf:first sg:person.0671747777.23
    256 rdf:rest N47a41ed270ac41a4a1ec0fdf665f90e2
    257 Na147b6837abc46a8a9f77312178d7234 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    258 schema:name Transcriptome
    259 rdf:type schema:DefinedTerm
    260 Na7b28073d076404da1d0afaeb3fcb634 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    261 schema:name Pluripotent Stem Cells
    262 rdf:type schema:DefinedTerm
    263 Na8f4299d86ef46ba85c39f9579d9784a rdf:first sg:person.01033041553.19
    264 rdf:rest N1a631b49af304bf58b7886c61bf84228
    265 Nac29447c23234ebf87c72f40bc207309 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    266 schema:name Tumor Suppressor Proteins
    267 rdf:type schema:DefinedTerm
    268 Nb1ccf1d40fb44d1f96fe83aef46993f1 rdf:first sg:person.01327773553.26
    269 rdf:rest Nf227cb944ba6465da6e36876a5b4f313
    270 Nb246f459b3974e81b89bc5bff9406391 rdf:first N3c46d9f6a28845618541846f23f4dee7
    271 rdf:rest N10905aba6a414333b30309bea93332e9
    272 Nb6f3b893cfe944048aac6d7f6ad2685f schema:issueNumber 1
    273 rdf:type schema:PublicationIssue
    274 Nb9247a6cb70147198a76e70983f9f724 rdf:first sg:person.011220302613.48
    275 rdf:rest Nc1669a50dd4c471ab11e11400004a310
    276 Nc1669a50dd4c471ab11e11400004a310 rdf:first sg:person.015345704751.25
    277 rdf:rest N597b6ddbbec54642a8e21312628bfaa9
    278 Nc1a2f907ba6949599f91629fd030610d rdf:first N2d828ac5f97743e7a08fa728bb54ee6a
    279 rdf:rest N674f681fc8ec4a679e961d30a3f252e6
    280 Ncb2712017fd047e788f12bafc6faddf5 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    281 schema:name Metabolic Networks and Pathways
    282 rdf:type schema:DefinedTerm
    283 Ncb67c402ca4b4d16ade0cb5496299520 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    284 schema:name Male
    285 rdf:type schema:DefinedTerm
    286 Ncca03bae063d40a9b1f05e5e082fd016 schema:affiliation grid-institutes:grid.17635.36
    287 schema:familyName Snoeys
    288 schema:givenName Jan
    289 rdf:type schema:Person
    290 Ncee626592311487fb76ddd9d83a88a82 schema:name pubmed_id
    291 schema:value 32170132
    292 rdf:type schema:PropertyValue
    293 Nd07f6fd02bae427498857a79ffb03f9b schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    294 schema:name Gene Knockout Techniques
    295 rdf:type schema:DefinedTerm
    296 Ndabebafcdfb146699b4a892bdfcdd9d8 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    297 schema:name Cell Line, Tumor
    298 rdf:type schema:DefinedTerm
    299 Ne83987768b924b14a0200ebd3d4d8c74 rdf:first sg:person.01267404401.45
    300 rdf:rest N058daa7550264e2895bfafa27cd5f86a
    301 Ne8d83c04f5e04818a809ed0fa8ef43d6 schema:name doi
    302 schema:value 10.1038/s41467-020-15058-6
    303 rdf:type schema:PropertyValue
    304 Nf227cb944ba6465da6e36876a5b4f313 rdf:first sg:person.016361550722.19
    305 rdf:rest N8f3ce00d2538421bb81d096df32a29bc
    306 Nf5020415bedd4ff481192879af5aa502 rdf:first Ncca03bae063d40a9b1f05e5e082fd016
    307 rdf:rest N193653d1a2cf457b83406bd1b51921c2
    308 Nfdc31c4aff6445d3b971fa8df9780322 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    309 schema:name Hepatocytes
    310 rdf:type schema:DefinedTerm
    311 anzsrc-for:06 schema:inDefinedTermSet anzsrc-for:
    312 schema:name Biological Sciences
    313 rdf:type schema:DefinedTerm
    314 anzsrc-for:0601 schema:inDefinedTermSet anzsrc-for:
    315 schema:name Biochemistry and Cell Biology
    316 rdf:type schema:DefinedTerm
    317 sg:grant.3939447 http://pending.schema.org/fundedItem sg:pub.10.1038/s41467-020-15058-6
    318 rdf:type schema:MonetaryGrant
    319 sg:grant.4456769 http://pending.schema.org/fundedItem sg:pub.10.1038/s41467-020-15058-6
    320 rdf:type schema:MonetaryGrant
    321 sg:grant.8508280 http://pending.schema.org/fundedItem sg:pub.10.1038/s41467-020-15058-6
    322 rdf:type schema:MonetaryGrant
    323 sg:grant.8514437 http://pending.schema.org/fundedItem sg:pub.10.1038/s41467-020-15058-6
    324 rdf:type schema:MonetaryGrant
    325 sg:journal.1043282 schema:issn 2041-1723
    326 schema:name Nature Communications
    327 schema:publisher Springer Nature
    328 rdf:type schema:Periodical
    329 sg:person.01033041553.19 schema:affiliation grid-institutes:grid.11486.3a
    330 schema:familyName Carmeliet
    331 schema:givenName Peter
    332 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01033041553.19
    333 rdf:type schema:Person
    334 sg:person.01037646713.05 schema:affiliation grid-institutes:grid.5596.f
    335 schema:familyName Verfaillie
    336 schema:givenName Catherine M.
    337 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01037646713.05
    338 rdf:type schema:Person
    339 sg:person.01054163573.07 schema:affiliation grid-institutes:grid.5596.f
    340 schema:familyName Cassiman
    341 schema:givenName David
    342 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01054163573.07
    343 rdf:type schema:Person
    344 sg:person.01064261433.49 schema:affiliation grid-institutes:grid.17635.36
    345 schema:familyName Hu
    346 schema:givenName Wei-Shou
    347 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01064261433.49
    348 rdf:type schema:Person
    349 sg:person.01114443415.72 schema:affiliation grid-institutes:grid.11205.37
    350 schema:familyName Ordovas
    351 schema:givenName Laura
    352 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01114443415.72
    353 rdf:type schema:Person
    354 sg:person.011220302613.48 schema:affiliation grid-institutes:grid.5596.f
    355 schema:familyName Rossi
    356 schema:givenName Matteo
    357 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.011220302613.48
    358 rdf:type schema:Person
    359 sg:person.01244040671.91 schema:affiliation grid-institutes:grid.5596.f
    360 schema:familyName Vanwelden
    361 schema:givenName Thomas
    362 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01244040671.91
    363 rdf:type schema:Person
    364 sg:person.01267404401.45 schema:affiliation grid-institutes:grid.7942.8
    365 schema:familyName Najimi
    366 schema:givenName Mustapha
    367 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01267404401.45
    368 rdf:type schema:Person
    369 sg:person.01305305435.04 schema:affiliation grid-institutes:grid.7942.8
    370 schema:familyName Sokal
    371 schema:givenName Etienne
    372 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01305305435.04
    373 rdf:type schema:Person
    374 sg:person.01313265732.75 schema:affiliation grid-institutes:grid.11486.3a
    375 schema:familyName Eelen
    376 schema:givenName Guy
    377 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01313265732.75
    378 rdf:type schema:Person
    379 sg:person.01327773553.26 schema:affiliation grid-institutes:grid.410569.f
    380 schema:familyName Roelandt
    381 schema:givenName Philip
    382 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01327773553.26
    383 rdf:type schema:Person
    384 sg:person.01360212631.05 schema:affiliation grid-institutes:grid.5596.f
    385 schema:familyName Kumar
    386 schema:givenName Manoj
    387 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01360212631.05
    388 rdf:type schema:Person
    389 sg:person.013605134364.50 schema:affiliation grid-institutes:grid.17635.36
    390 schema:familyName One
    391 schema:givenName Jennifer
    392 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.013605134364.50
    393 rdf:type schema:Person
    394 sg:person.015345704751.25 schema:affiliation grid-institutes:grid.5596.f
    395 schema:familyName Vazquez
    396 schema:givenName Marta Aguirre
    397 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.015345704751.25
    398 rdf:type schema:Person
    399 sg:person.016136204453.32 schema:affiliation grid-institutes:grid.5596.f
    400 schema:familyName Tricot
    401 schema:givenName Tine
    402 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.016136204453.32
    403 rdf:type schema:Person
    404 sg:person.016174635653.11 schema:affiliation grid-institutes:grid.7942.8
    405 schema:familyName Taghdouini
    406 schema:givenName Adil El
    407 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.016174635653.11
    408 rdf:type schema:Person
    409 sg:person.016273370760.93 schema:affiliation grid-institutes:grid.5596.f
    410 schema:familyName Chesnais
    411 schema:givenName François
    412 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.016273370760.93
    413 rdf:type schema:Person
    414 sg:person.016361550722.19 schema:affiliation grid-institutes:grid.5596.f
    415 schema:familyName Doglioni
    416 schema:givenName Ginevra
    417 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.016361550722.19
    418 rdf:type schema:Person
    419 sg:person.0620030745.13 schema:affiliation grid-institutes:grid.5596.f
    420 schema:familyName Fendt
    421 schema:givenName Sarah-Maria
    422 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0620030745.13
    423 rdf:type schema:Person
    424 sg:person.0654416175.72 schema:affiliation grid-institutes:grid.5596.f
    425 schema:familyName Vriens
    426 schema:givenName Kim
    427 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0654416175.72
    428 rdf:type schema:Person
    429 sg:person.0671747777.23 schema:affiliation grid-institutes:grid.5596.f
    430 schema:familyName Boon
    431 schema:givenName Ruben
    432 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0671747777.23
    433 rdf:type schema:Person
    434 sg:person.0704536050.07 schema:affiliation grid-institutes:grid.5596.f
    435 schema:familyName Bird
    436 schema:givenName Matthew
    437 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0704536050.07
    438 rdf:type schema:Person
    439 sg:person.0707254600.80 schema:affiliation grid-institutes:grid.5596.f
    440 schema:familyName Elia
    441 schema:givenName Ilaria
    442 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0707254600.80
    443 rdf:type schema:Person
    444 sg:pub.10.1007/978-1-62703-125-7_17 schema:sameAs https://app.dimensions.ai/details/publication/pub.1005738391
    445 https://doi.org/10.1007/978-1-62703-125-7_17
    446 rdf:type schema:CreativeWork
    447 sg:pub.10.1007/978-1-62703-348-0_11 schema:sameAs https://app.dimensions.ai/details/publication/pub.1011996516
    448 https://doi.org/10.1007/978-1-62703-348-0_11
    449 rdf:type schema:CreativeWork
    450 sg:pub.10.1007/bf02634571 schema:sameAs https://app.dimensions.ai/details/publication/pub.1024847488
    451 https://doi.org/10.1007/bf02634571
    452 rdf:type schema:CreativeWork
    453 sg:pub.10.1007/s00204-016-1745-4 schema:sameAs https://app.dimensions.ai/details/publication/pub.1039080201
    454 https://doi.org/10.1007/s00204-016-1745-4
    455 rdf:type schema:CreativeWork
    456 sg:pub.10.1007/s00204-016-1761-4 schema:sameAs https://app.dimensions.ai/details/publication/pub.1013698897
    457 https://doi.org/10.1007/s00204-016-1761-4
    458 rdf:type schema:CreativeWork
    459 sg:pub.10.1007/s10565-017-9383-z schema:sameAs https://app.dimensions.ai/details/publication/pub.1083400234
    460 https://doi.org/10.1007/s10565-017-9383-z
    461 rdf:type schema:CreativeWork
    462 sg:pub.10.1007/s10911-016-9354-7 schema:sameAs https://app.dimensions.ai/details/publication/pub.1011341548
    463 https://doi.org/10.1007/s10911-016-9354-7
    464 rdf:type schema:CreativeWork
    465 sg:pub.10.1007/s11306-011-0284-5 schema:sameAs https://app.dimensions.ai/details/publication/pub.1051861558
    466 https://doi.org/10.1007/s11306-011-0284-5
    467 rdf:type schema:CreativeWork
    468 sg:pub.10.1038/cr.2012.144 schema:sameAs https://app.dimensions.ai/details/publication/pub.1029165674
    469 https://doi.org/10.1038/cr.2012.144
    470 rdf:type schema:CreativeWork
    471 sg:pub.10.1038/nature06322 schema:sameAs https://app.dimensions.ai/details/publication/pub.1010205458
    472 https://doi.org/10.1038/nature06322
    473 rdf:type schema:CreativeWork
    474 sg:pub.10.1038/nature12271 schema:sameAs https://app.dimensions.ai/details/publication/pub.1034831733
    475 https://doi.org/10.1038/nature12271
    476 rdf:type schema:CreativeWork
    477 sg:pub.10.1038/nbt.2786 schema:sameAs https://app.dimensions.ai/details/publication/pub.1013732820
    478 https://doi.org/10.1038/nbt.2786
    479 rdf:type schema:CreativeWork
    480 sg:pub.10.1038/nbt.3377 schema:sameAs https://app.dimensions.ai/details/publication/pub.1033847015
    481 https://doi.org/10.1038/nbt.3377
    482 rdf:type schema:CreativeWork
    483 sg:pub.10.1038/nbt.4101 schema:sameAs https://app.dimensions.ai/details/publication/pub.1103157300
    484 https://doi.org/10.1038/nbt.4101
    485 rdf:type schema:CreativeWork
    486 sg:pub.10.1038/nbt1361 schema:sameAs https://app.dimensions.ai/details/publication/pub.1045539531
    487 https://doi.org/10.1038/nbt1361
    488 rdf:type schema:CreativeWork
    489 sg:pub.10.1038/ncb3272 schema:sameAs https://app.dimensions.ai/details/publication/pub.1032287924
    490 https://doi.org/10.1038/ncb3272
    491 rdf:type schema:CreativeWork
    492 sg:pub.10.1038/nchembio.364 schema:sameAs https://app.dimensions.ai/details/publication/pub.1020884064
    493 https://doi.org/10.1038/nchembio.364
    494 rdf:type schema:CreativeWork
    495 sg:pub.10.1038/ncomms15267 schema:sameAs https://app.dimensions.ai/details/publication/pub.1085389814
    496 https://doi.org/10.1038/ncomms15267
    497 rdf:type schema:CreativeWork
    498 sg:pub.10.1038/nm815 schema:sameAs https://app.dimensions.ai/details/publication/pub.1016854060
    499 https://doi.org/10.1038/nm815
    500 rdf:type schema:CreativeWork
    501 sg:pub.10.1038/nprot.2015.128 schema:sameAs https://app.dimensions.ai/details/publication/pub.1025360205
    502 https://doi.org/10.1038/nprot.2015.128
    503 rdf:type schema:CreativeWork
    504 sg:pub.10.1038/s42255-019-0054-7 schema:sameAs https://app.dimensions.ai/details/publication/pub.1113305931
    505 https://doi.org/10.1038/s42255-019-0054-7
    506 rdf:type schema:CreativeWork
    507 sg:pub.10.1038/s42255-019-0082-3 schema:sameAs https://app.dimensions.ai/details/publication/pub.1117823480
    508 https://doi.org/10.1038/s42255-019-0082-3
    509 rdf:type schema:CreativeWork
    510 sg:pub.10.1038/s42255-019-0124-x schema:sameAs https://app.dimensions.ai/details/publication/pub.1121787070
    511 https://doi.org/10.1038/s42255-019-0124-x
    512 rdf:type schema:CreativeWork
    513 sg:pub.10.1038/s42255-019-0137-5 schema:sameAs https://app.dimensions.ai/details/publication/pub.1122475460
    514 https://doi.org/10.1038/s42255-019-0137-5
    515 rdf:type schema:CreativeWork
    516 sg:pub.10.1038/sj.onc.1209106 schema:sameAs https://app.dimensions.ai/details/publication/pub.1034184478
    517 https://doi.org/10.1038/sj.onc.1209106
    518 rdf:type schema:CreativeWork
    519 sg:pub.10.1038/srep25187 schema:sameAs https://app.dimensions.ai/details/publication/pub.1028498125
    520 https://doi.org/10.1038/srep25187
    521 rdf:type schema:CreativeWork
    522 sg:pub.10.1186/1471-2105-9-559 schema:sameAs https://app.dimensions.ai/details/publication/pub.1020312314
    523 https://doi.org/10.1186/1471-2105-9-559
    524 rdf:type schema:CreativeWork
    525 sg:pub.10.1186/s13059-020-1934-6 schema:sameAs https://app.dimensions.ai/details/publication/pub.1124677203
    526 https://doi.org/10.1186/s13059-020-1934-6
    527 rdf:type schema:CreativeWork
    528 grid-institutes:grid.11205.37 schema:alternateName Present Address: Biomedical Signal Interpretation and Computational Simulation (BSICoS) Group, Aragón Institute of Engineering Research, IIS Aragón University of Zaragoza, Aragon I + D Foundation (ARAID), Zaragoza, Spain
    529 schema:name Department of Development and Regeneration, Stem Cell Institute, KU Leuven, Leuven, Belgium
    530 Present Address: Biomedical Signal Interpretation and Computational Simulation (BSICoS) Group, Aragón Institute of Engineering Research, IIS Aragón University of Zaragoza, Aragon I + D Foundation (ARAID), Zaragoza, Spain
    531 rdf:type schema:Organization
    532 grid-institutes:grid.11486.3a schema:alternateName Laboratory of Angiogenesis and Vascular Metabolism, Center of Cancer Biology, VIB, Leuven, Belgium
    533 schema:name Laboratory of Angiogenesis and Vascular Metabolism, Center of Cancer Biology, VIB, Leuven, Belgium
    534 Laboratory of Angiogenesis and Vascular Metabolism, Department of Oncology, KU Leuven, Leuven, Belgium
    535 rdf:type schema:Organization
    536 grid-institutes:grid.17635.36 schema:alternateName Stem Cell Institute, University of Minnesota, Minneapolis, MN USA
    537 schema:name Department of Chemical Engineering and Materials Science, University of Minnesota, Minneapolis, MN USA
    538 Stem Cell Institute, University of Minnesota, Minneapolis, MN USA
    539 rdf:type schema:Organization
    540 grid-institutes:grid.410569.f schema:alternateName Present Address: Department of Gastroenterology and Hepatology, UZ Leuven, Leuven, Belgium
    541 schema:name Department of Development and Regeneration, Stem Cell Institute, KU Leuven, Leuven, Belgium
    542 Hepatology, Department of Clinical and Experimental Medicine, KU Leuven, Leuven, Belgium
    543 Present Address: Department of Gastroenterology and Hepatology, UZ Leuven, Leuven, Belgium
    544 Present Address: Translational Research in GastroIntestinal Disorders (TARGID), Department of Chronic Diseases, Metabolism and Ageing (CHROMETA), KU Leuven, Leuven, Belgium
    545 rdf:type schema:Organization
    546 grid-institutes:grid.419619.2 schema:alternateName Janssen Research and Development, Beerse, Belgium
    547 schema:name Janssen Research and Development, Beerse, Belgium
    548 rdf:type schema:Organization
    549 grid-institutes:grid.5596.f schema:alternateName Department of Development and Regeneration, Stem Cell Institute, KU Leuven, Leuven, Belgium
    550 Hepatology, Department of Clinical and Experimental Medicine, KU Leuven, Leuven, Belgium
    551 Laboratory of Cellular Metabolism and Metabolic Regulation, Department of Oncology, KU Leuven and Leuven Cancer Institute (LKI), Leuven, Belgium
    552 schema:name Department of Development and Regeneration, Stem Cell Institute, KU Leuven, Leuven, Belgium
    553 Hepatology, Department of Clinical and Experimental Medicine, KU Leuven, Leuven, Belgium
    554 Laboratory of Cellular Metabolism and Metabolic Regulation, Department of Oncology, KU Leuven and Leuven Cancer Institute (LKI), Leuven, Belgium
    555 Laboratory of Cellular Metabolism and Metabolic Regulation, VIB Center for Cancer Biology, VIB, Leuven, Belgium
    556 rdf:type schema:Organization
    557 grid-institutes:grid.7942.8 schema:alternateName Laboratory of Pediatric Hepatology and Cell Therapy, Universit Catholique de Louvain & Cliniques Universitaires St Luc, Institut de Recherche Clinique et Expérimentale (IREC), Brussels, Belgium
    558 schema:name Laboratory of Pediatric Hepatology and Cell Therapy, Universit Catholique de Louvain & Cliniques Universitaires St Luc, Institut de Recherche Clinique et Expérimentale (IREC), Brussels, Belgium
    559 rdf:type schema:Organization
     




    Preview window. Press ESC to close (or click here)


    ...