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
  • 2007-11-29. 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": "Biomedical Signal Interpretation and Computational Simulation (BSICoS) Group, Arag\u00f3n Institute of Engineering Research, IIS Arag\u00f3n University of Zaragoza, Aragon I\u2009+\u2009D 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", 
                "Biomedical Signal Interpretation and Computational Simulation (BSICoS) Group, Arag\u00f3n Institute of Engineering Research, IIS Arag\u00f3n University of Zaragoza, Aragon I\u2009+\u2009D 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": "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", 
                "Translational Research in GastroIntestinal Disorders (TARGID), Department of Chronic Diseases, Metabolism and Ageing (CHROMETA), KU Leuven, Leuven, Belgium", 
                "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": "El Taghdouini", 
            "givenName": "Adil", 
            "id": "sg:person.014730332147.46", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.014730332147.46"
            ], 
            "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.10.1038/nature12271", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1034831733", 
              "https://doi.org/10.1038/nature12271"
            ], 
            "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.10.1038/ncb3272", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1032287924", 
              "https://doi.org/10.1038/ncb3272"
            ], 
            "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/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.10.1038/srep25187", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1028498125", 
              "https://doi.org/10.1038/srep25187"
            ], 
            "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.10.1007/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/nature06322", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1010205458", 
              "https://doi.org/10.1038/nature06322"
            ], 
            "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.10.1007/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.10.1007/bf02634571", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1024847488", 
              "https://doi.org/10.1007/bf02634571"
            ], 
            "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/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.10.1007/978-1-62703-348-0_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.3377", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1033847015", 
              "https://doi.org/10.1038/nbt.3377"
            ], 
            "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.10.1007/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.10.1186/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.10.1186/1471-2105-9-559", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1020312314", 
              "https://doi.org/10.1186/1471-2105-9-559"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1007/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.10.1038/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.10.1038/nbt.4101", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1103157300", 
              "https://doi.org/10.1038/nbt.4101"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/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.10.1007/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.10.1038/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/nbt1361", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1045539531", 
              "https://doi.org/10.1038/nbt1361"
            ], 
            "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"
          }
        ], 
        "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.4456769", 
            "type": "MonetaryGrant"
          }, 
          {
            "id": "sg:grant.3939447", 
            "type": "MonetaryGrant"
          }, 
          {
            "id": "sg:grant.8508280", 
            "type": "MonetaryGrant"
          }, 
          {
            "id": "sg:grant.8514437", 
            "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", 
          "amino acid levels", 
          "extracellular nutrients", 
          "stem cell-derived hepatocyte-like cells", 
          "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", 
          "cellular maturity", 
          "liver injury", 
          "biotransformation capacity", 
          "preclinical setting", 
          "cells", 
          "human hepatocytes", 
          "drug biotransformation", 
          "hepatic functionality", 
          "metabolism", 
          "acid levels", 
          "major determinant", 
          "lineages", 
          "nutritional needs", 
          "regulator", 
          "hepatocytes", 
          "differentiation", 
          "acid", 
          "high levels", 
          "nutrients", 
          "levels", 
          "function", 
          "injury", 
          "biotransformation", 
          "maturity", 
          "lines", 
          "conclusion", 
          "setting", 
          "determinants", 
          "sensitivity", 
          "profile", 
          "acquisition", 
          "need", 
          "capacity", 
          "data", 
          "functionality", 
          "independence"
        ], 
        "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": "2022-05-20T07:37", 
        "sdLicense": "https://scigraph.springernature.com/explorer/license/", 
        "sdPublisher": {
          "name": "Springer Nature - SN SciGraph project", 
          "type": "Organization"
        }, 
        "sdSource": "s3://com-springernature-scigraph/baseset/20220519/entities/gbq_results/article/article_854.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.

    553 TRIPLES      22 PREDICATES      138 URIs      102 LITERALS      32 BLANK NODES

    Subject Predicate Object
    1 sg:pub.10.1038/s41467-020-15058-6 schema:about N0aa6c1453aba424ebd291eb50d4dddb6
    2 N117db20d69bf4435b83102edea0bde53
    3 N11e9c680d5704b28a4a42378af3e04fd
    4 N17c14bec9df9417eb2ec169618f41127
    5 N21d3bf3aa4f047b8adcb7827094b191a
    6 N3482a20a7abb4b59a0064a8c69ee4c10
    7 N5949d145352442b0951568b7902ea7d9
    8 N5f1aa1df4f33400bb09172532b84e08c
    9 N6fc21c31d75748029f026c4e5f08d2e7
    10 N7684aea64d9c4eed86fb03caef5769f5
    11 N8d4dc829abf24aeaa389e9da76abc648
    12 N9e75456e7aa04761a609281bc8e779fd
    13 Na869f09ad6fa48c3aa3cfb94aed389d8
    14 Nabf5d7a7bc2e4ed8b2cd6101adc83d10
    15 Nb3565f9dd039474a84a09f3b750ad128
    16 Nbd229918e5194e8fa6cd7b8e76828a82
    17 Nc6180104657b4ff39ae7dfbf15bd2b36
    18 Ncfcd811eff3e4d8b9fba25e7ea597a1c
    19 Nd1dd765befa14f0392737d517a11acf4
    20 Nd972bfcca4224591840d5fae8f306fa4
    21 Nddf57d1e11ad4529bf104994675042a5
    22 Nee19d358fa994e838898510fcc1c8c14
    23 Nf48cb9fe599f47e5b61ff26caf81a438
    24 Nf57e9a4996f24e46b49c7d59080c468c
    25 Nf9d8dd950600472e8f2583767948530e
    26 anzsrc-for:06
    27 anzsrc-for:0601
    28 schema:author N98dee9747525494ebcaa6a8d6aaaa6c3
    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 N8abd5ac190b74fada899a0f3f31f4136
    64 Nbc2d9d7f20514482ad84e1277c595cd4
    65 sg:journal.1043282
    66 schema:keywords HepG2 cells
    67 acid
    68 acid levels
    69 acquisition
    70 amino acid levels
    71 amino acids
    72 biotransformation
    73 biotransformation capacity
    74 capacity
    75 cell differentiation
    76 cell lines
    77 cell-derived hepatocyte-like cells
    78 cells
    79 cellular maturity
    80 cellular metabolism
    81 conclusion
    82 cultured primary human hepatocytes
    83 data
    84 determinants
    85 developmental regulators
    86 differentiation
    87 drug biotransformation
    88 drug-induced liver injury
    89 extracellular amino acids
    90 extracellular nutrient levels
    91 extracellular nutrients
    92 function
    93 functionality
    94 hepatic functionality
    95 hepatic lineage
    96 hepatocyte-like cells
    97 hepatocytes
    98 hepatoma cell line
    99 hepatoma cells
    100 high levels
    101 human hepatocytes
    102 independence
    103 injury
    104 levels
    105 lineages
    106 lines
    107 liver injury
    108 major determinant
    109 maturity
    110 metabolism
    111 mitochondrial function
    112 need
    113 nutrient levels
    114 nutrients
    115 nutritional needs
    116 preclinical setting
    117 primary human hepatocytes
    118 profile
    119 regulator
    120 sensitivity
    121 setting
    122 stem cell differentiation
    123 stem cell-derived hepatocyte-like cells
    124 transcriptional profiles
    125 schema:name Amino acid levels determine metabolism and CYP450 function of hepatocytes and hepatoma cell lines
    126 schema:pagination 1393
    127 schema:productId N0236fb4308c84d29908c0ad56f7df2f7
    128 N38f4acaa86934c3bb96450245090cbce
    129 N8545bef300ea49019559735fee70e0e5
    130 schema:sameAs https://app.dimensions.ai/details/publication/pub.1125612547
    131 https://doi.org/10.1038/s41467-020-15058-6
    132 schema:sdDatePublished 2022-05-20T07:37
    133 schema:sdLicense https://scigraph.springernature.com/explorer/license/
    134 schema:sdPublisher Nde3a68f923af4b9e9a935ce6fea00aa0
    135 schema:url https://doi.org/10.1038/s41467-020-15058-6
    136 sgo:license sg:explorer/license/
    137 sgo:sdDataset articles
    138 rdf:type schema:ScholarlyArticle
    139 N0236fb4308c84d29908c0ad56f7df2f7 schema:name doi
    140 schema:value 10.1038/s41467-020-15058-6
    141 rdf:type schema:PropertyValue
    142 N063030a91e204571b7e6bfd7284eecb4 rdf:first sg:person.01064261433.49
    143 rdf:rest Nf59becf282d9403c9304e925bfd2b68f
    144 N0981f462135544abbc06ee6c3c2288e9 schema:affiliation grid-institutes:grid.17635.36
    145 schema:familyName Monshouwer
    146 schema:givenName Mario
    147 rdf:type schema:Person
    148 N0aa6c1453aba424ebd291eb50d4dddb6 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    149 schema:name Transcriptome
    150 rdf:type schema:DefinedTerm
    151 N117db20d69bf4435b83102edea0bde53 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    152 schema:name Metabolic Networks and Pathways
    153 rdf:type schema:DefinedTerm
    154 N11e9c680d5704b28a4a42378af3e04fd schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    155 schema:name Pluripotent Stem Cells
    156 rdf:type schema:DefinedTerm
    157 N135f52a7e9984048a6e7897b11c567d8 rdf:first sg:person.01327773553.26
    158 rdf:rest Nb4c9eb246a4145efb4cee6d677a80ad6
    159 N17c14bec9df9417eb2ec169618f41127 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    160 schema:name High-Throughput Screening Assays
    161 rdf:type schema:DefinedTerm
    162 N21d3bf3aa4f047b8adcb7827094b191a schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    163 schema:name Middle Aged
    164 rdf:type schema:DefinedTerm
    165 N2e4fa291d3a64601895494b2da0aff8d rdf:first N7c7436bd4ed7481d80e8c4f1f427b8ef
    166 rdf:rest Nfd04571d423c4466bf4ce691e6c95912
    167 N30f8842a55174bd3ae577a2cf3b1d5bf rdf:first sg:person.01305305435.04
    168 rdf:rest Na9d3e569062143c0af3ae7a649acc6df
    169 N3482a20a7abb4b59a0064a8c69ee4c10 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    170 schema:name Gene Knockout Techniques
    171 rdf:type schema:DefinedTerm
    172 N37b7040297e2441ea863841007c09dfe rdf:first sg:person.014730332147.46
    173 rdf:rest Nc4772f9cefb3434d9ee0ddc2fe53e1df
    174 N38f4acaa86934c3bb96450245090cbce schema:name pubmed_id
    175 schema:value 32170132
    176 rdf:type schema:PropertyValue
    177 N45b89595d2eb47c092865d715d2047b8 schema:affiliation grid-institutes:grid.11486.3a
    178 schema:familyName Lange
    179 schema:givenName Christian
    180 rdf:type schema:Person
    181 N550f9ab842c94029bed9e102e002282d rdf:first sg:person.0707254600.80
    182 rdf:rest Nc34112aac49a4b75825ec23e9da1528b
    183 N57342c9e79ee4a20a80ef9d26f3e5dda rdf:first sg:person.016136204453.32
    184 rdf:rest N550f9ab842c94029bed9e102e002282d
    185 N5949d145352442b0951568b7902ea7d9 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    186 schema:name Carcinoma, Hepatocellular
    187 rdf:type schema:DefinedTerm
    188 N5ca448dea59b42c688d819b92ec1e3b6 rdf:first sg:person.015345704751.25
    189 rdf:rest N7b839a7dff1c4c6a86e649aea6d35d82
    190 N5f1aa1df4f33400bb09172532b84e08c schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    191 schema:name Stem Cells
    192 rdf:type schema:DefinedTerm
    193 N6fc21c31d75748029f026c4e5f08d2e7 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    194 schema:name Cell Line, Tumor
    195 rdf:type schema:DefinedTerm
    196 N74c3c918952d44f9b0130f80891dbaa1 rdf:first Nc3394d7eaf4c47f689449572d076f6b8
    197 rdf:rest Nb7f24f9084274d28b174716a5fc8a191
    198 N7684aea64d9c4eed86fb03caef5769f5 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    199 schema:name Hepatocyte Nuclear Factor 1-alpha
    200 rdf:type schema:DefinedTerm
    201 N79f5e6e1d122426196d58b23a7215138 rdf:first sg:person.013605134364.50
    202 rdf:rest N2e4fa291d3a64601895494b2da0aff8d
    203 N7b54d7e517744d40a48bfc4dba5cf272 rdf:first sg:person.01037646713.05
    204 rdf:rest rdf:nil
    205 N7b839a7dff1c4c6a86e649aea6d35d82 rdf:first sg:person.01244040671.91
    206 rdf:rest N9151c717f5a1481ebbcaf60fab8c9182
    207 N7c7436bd4ed7481d80e8c4f1f427b8ef schema:affiliation grid-institutes:grid.5596.f
    208 schema:familyName De Smedt
    209 schema:givenName Jonathan
    210 rdf:type schema:Person
    211 N8545bef300ea49019559735fee70e0e5 schema:name dimensions_id
    212 schema:value pub.1125612547
    213 rdf:type schema:PropertyValue
    214 N8abd5ac190b74fada899a0f3f31f4136 schema:issueNumber 1
    215 rdf:type schema:PublicationIssue
    216 N8d4dc829abf24aeaa389e9da76abc648 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    217 schema:name Hep G2 Cells
    218 rdf:type schema:DefinedTerm
    219 N9151c717f5a1481ebbcaf60fab8c9182 rdf:first sg:person.016273370760.93
    220 rdf:rest N37b7040297e2441ea863841007c09dfe
    221 N98dee9747525494ebcaa6a8d6aaaa6c3 rdf:first sg:person.0671747777.23
    222 rdf:rest Nba28d7114eaf45dcaabc605ae8775d09
    223 N99391fdceba4468dab2bea6d6239059c rdf:first sg:person.011220302613.48
    224 rdf:rest N5ca448dea59b42c688d819b92ec1e3b6
    225 N99f6c36cee4f4fbbb63b4bc1a66f0bcb schema:affiliation grid-institutes:grid.419619.2
    226 schema:familyName Jacobs
    227 schema:givenName Frank
    228 rdf:type schema:Person
    229 N9bafe2066f4f437393408421ad1f53dc rdf:first sg:person.0654416175.72
    230 rdf:rest N99391fdceba4468dab2bea6d6239059c
    231 N9ddb8949c8d14f508e28619ba490e799 rdf:first N99f6c36cee4f4fbbb63b4bc1a66f0bcb
    232 rdf:rest N79f5e6e1d122426196d58b23a7215138
    233 N9e75456e7aa04761a609281bc8e779fd schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    234 schema:name Cytochrome P-450 CYP3A
    235 rdf:type schema:DefinedTerm
    236 Na023258c250340e7ba0d9f9b2eb0b5c7 rdf:first sg:person.01033041553.19
    237 rdf:rest Na9f7a552988e4cb08320ba8da19058dd
    238 Na869f09ad6fa48c3aa3cfb94aed389d8 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    239 schema:name Tumor Suppressor Proteins
    240 rdf:type schema:DefinedTerm
    241 Na9d3e569062143c0af3ae7a649acc6df rdf:first sg:person.01054163573.07
    242 rdf:rest N74c3c918952d44f9b0130f80891dbaa1
    243 Na9f7a552988e4cb08320ba8da19058dd rdf:first sg:person.0620030745.13
    244 rdf:rest N7b54d7e517744d40a48bfc4dba5cf272
    245 Nabf5d7a7bc2e4ed8b2cd6101adc83d10 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    246 schema:name Hepatocyte Nuclear Factor 3-gamma
    247 rdf:type schema:DefinedTerm
    248 Nb3565f9dd039474a84a09f3b750ad128 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    249 schema:name Male
    250 rdf:type schema:DefinedTerm
    251 Nb4c9eb246a4145efb4cee6d677a80ad6 rdf:first sg:person.016361550722.19
    252 rdf:rest N9bafe2066f4f437393408421ad1f53dc
    253 Nb7f24f9084274d28b174716a5fc8a191 rdf:first N0981f462135544abbc06ee6c3c2288e9
    254 rdf:rest N063030a91e204571b7e6bfd7284eecb4
    255 Nba28d7114eaf45dcaabc605ae8775d09 rdf:first sg:person.01360212631.05
    256 rdf:rest N57342c9e79ee4a20a80ef9d26f3e5dda
    257 Nbc2d9d7f20514482ad84e1277c595cd4 schema:volumeNumber 11
    258 rdf:type schema:PublicationVolume
    259 Nbd229918e5194e8fa6cd7b8e76828a82 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    260 schema:name Liver
    261 rdf:type schema:DefinedTerm
    262 Nc3394d7eaf4c47f689449572d076f6b8 schema:affiliation grid-institutes:grid.17635.36
    263 schema:familyName Snoeys
    264 schema:givenName Jan
    265 rdf:type schema:Person
    266 Nc34112aac49a4b75825ec23e9da1528b rdf:first sg:person.01114443415.72
    267 rdf:rest N9ddb8949c8d14f508e28619ba490e799
    268 Nc4772f9cefb3434d9ee0ddc2fe53e1df rdf:first sg:person.01267404401.45
    269 rdf:rest N30f8842a55174bd3ae577a2cf3b1d5bf
    270 Nc6180104657b4ff39ae7dfbf15bd2b36 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    271 schema:name Liver Neoplasms
    272 rdf:type schema:DefinedTerm
    273 Ncfcd811eff3e4d8b9fba25e7ea597a1c schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    274 schema:name Amino Acids
    275 rdf:type schema:DefinedTerm
    276 Nd1dd765befa14f0392737d517a11acf4 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    277 schema:name Hepatocytes
    278 rdf:type schema:DefinedTerm
    279 Nd972bfcca4224591840d5fae8f306fa4 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    280 schema:name Cell Differentiation
    281 rdf:type schema:DefinedTerm
    282 Nd98197d95e4f4252819f449f862ca42e rdf:first sg:person.0704536050.07
    283 rdf:rest N135f52a7e9984048a6e7897b11c567d8
    284 Nddf57d1e11ad4529bf104994675042a5 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    285 schema:name Homeodomain Proteins
    286 rdf:type schema:DefinedTerm
    287 Nde3a68f923af4b9e9a935ce6fea00aa0 schema:name Springer Nature - SN SciGraph project
    288 rdf:type schema:Organization
    289 Nee19d358fa994e838898510fcc1c8c14 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    290 schema:name Metabolic Engineering
    291 rdf:type schema:DefinedTerm
    292 Nf48cb9fe599f47e5b61ff26caf81a438 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    293 schema:name Cytochrome P-450 Enzyme System
    294 rdf:type schema:DefinedTerm
    295 Nf57e9a4996f24e46b49c7d59080c468c schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    296 schema:name Female
    297 rdf:type schema:DefinedTerm
    298 Nf59becf282d9403c9304e925bfd2b68f rdf:first N45b89595d2eb47c092865d715d2047b8
    299 rdf:rest Na023258c250340e7ba0d9f9b2eb0b5c7
    300 Nf9d8dd950600472e8f2583767948530e schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    301 schema:name Humans
    302 rdf:type schema:DefinedTerm
    303 Nfd04571d423c4466bf4ce691e6c95912 rdf:first sg:person.01313265732.75
    304 rdf:rest Nd98197d95e4f4252819f449f862ca42e
    305 anzsrc-for:06 schema:inDefinedTermSet anzsrc-for:
    306 schema:name Biological Sciences
    307 rdf:type schema:DefinedTerm
    308 anzsrc-for:0601 schema:inDefinedTermSet anzsrc-for:
    309 schema:name Biochemistry and Cell Biology
    310 rdf:type schema:DefinedTerm
    311 sg:grant.3939447 http://pending.schema.org/fundedItem sg:pub.10.1038/s41467-020-15058-6
    312 rdf:type schema:MonetaryGrant
    313 sg:grant.4456769 http://pending.schema.org/fundedItem sg:pub.10.1038/s41467-020-15058-6
    314 rdf:type schema:MonetaryGrant
    315 sg:grant.8508280 http://pending.schema.org/fundedItem sg:pub.10.1038/s41467-020-15058-6
    316 rdf:type schema:MonetaryGrant
    317 sg:grant.8514437 http://pending.schema.org/fundedItem sg:pub.10.1038/s41467-020-15058-6
    318 rdf:type schema:MonetaryGrant
    319 sg:journal.1043282 schema:issn 2041-1723
    320 schema:name Nature Communications
    321 schema:publisher Springer Nature
    322 rdf:type schema:Periodical
    323 sg:person.01033041553.19 schema:affiliation grid-institutes:grid.11486.3a
    324 schema:familyName Carmeliet
    325 schema:givenName Peter
    326 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01033041553.19
    327 rdf:type schema:Person
    328 sg:person.01037646713.05 schema:affiliation grid-institutes:grid.5596.f
    329 schema:familyName Verfaillie
    330 schema:givenName Catherine M.
    331 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01037646713.05
    332 rdf:type schema:Person
    333 sg:person.01054163573.07 schema:affiliation grid-institutes:grid.5596.f
    334 schema:familyName Cassiman
    335 schema:givenName David
    336 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01054163573.07
    337 rdf:type schema:Person
    338 sg:person.01064261433.49 schema:affiliation grid-institutes:grid.17635.36
    339 schema:familyName Hu
    340 schema:givenName Wei-Shou
    341 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01064261433.49
    342 rdf:type schema:Person
    343 sg:person.01114443415.72 schema:affiliation grid-institutes:grid.11205.37
    344 schema:familyName Ordovas
    345 schema:givenName Laura
    346 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01114443415.72
    347 rdf:type schema:Person
    348 sg:person.011220302613.48 schema:affiliation grid-institutes:grid.5596.f
    349 schema:familyName Rossi
    350 schema:givenName Matteo
    351 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.011220302613.48
    352 rdf:type schema:Person
    353 sg:person.01244040671.91 schema:affiliation grid-institutes:grid.5596.f
    354 schema:familyName Vanwelden
    355 schema:givenName Thomas
    356 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01244040671.91
    357 rdf:type schema:Person
    358 sg:person.01267404401.45 schema:affiliation grid-institutes:grid.7942.8
    359 schema:familyName Najimi
    360 schema:givenName Mustapha
    361 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01267404401.45
    362 rdf:type schema:Person
    363 sg:person.01305305435.04 schema:affiliation grid-institutes:grid.7942.8
    364 schema:familyName Sokal
    365 schema:givenName Etienne
    366 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01305305435.04
    367 rdf:type schema:Person
    368 sg:person.01313265732.75 schema:affiliation grid-institutes:grid.11486.3a
    369 schema:familyName Eelen
    370 schema:givenName Guy
    371 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01313265732.75
    372 rdf:type schema:Person
    373 sg:person.01327773553.26 schema:affiliation grid-institutes:grid.410569.f
    374 schema:familyName Roelandt
    375 schema:givenName Philip
    376 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01327773553.26
    377 rdf:type schema:Person
    378 sg:person.01360212631.05 schema:affiliation grid-institutes:grid.5596.f
    379 schema:familyName Kumar
    380 schema:givenName Manoj
    381 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01360212631.05
    382 rdf:type schema:Person
    383 sg:person.013605134364.50 schema:affiliation grid-institutes:grid.17635.36
    384 schema:familyName One
    385 schema:givenName Jennifer
    386 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.013605134364.50
    387 rdf:type schema:Person
    388 sg:person.014730332147.46 schema:affiliation grid-institutes:grid.7942.8
    389 schema:familyName El Taghdouini
    390 schema:givenName Adil
    391 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.014730332147.46
    392 rdf:type schema:Person
    393 sg:person.015345704751.25 schema:affiliation grid-institutes:grid.5596.f
    394 schema:familyName Vazquez
    395 schema:givenName Marta Aguirre
    396 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.015345704751.25
    397 rdf:type schema:Person
    398 sg:person.016136204453.32 schema:affiliation grid-institutes:grid.5596.f
    399 schema:familyName Tricot
    400 schema:givenName Tine
    401 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.016136204453.32
    402 rdf:type schema:Person
    403 sg:person.016273370760.93 schema:affiliation grid-institutes:grid.5596.f
    404 schema:familyName Chesnais
    405 schema:givenName François
    406 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.016273370760.93
    407 rdf:type schema:Person
    408 sg:person.016361550722.19 schema:affiliation grid-institutes:grid.5596.f
    409 schema:familyName Doglioni
    410 schema:givenName Ginevra
    411 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.016361550722.19
    412 rdf:type schema:Person
    413 sg:person.0620030745.13 schema:affiliation grid-institutes:grid.5596.f
    414 schema:familyName Fendt
    415 schema:givenName Sarah-Maria
    416 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0620030745.13
    417 rdf:type schema:Person
    418 sg:person.0654416175.72 schema:affiliation grid-institutes:grid.5596.f
    419 schema:familyName Vriens
    420 schema:givenName Kim
    421 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0654416175.72
    422 rdf:type schema:Person
    423 sg:person.0671747777.23 schema:affiliation grid-institutes:grid.5596.f
    424 schema:familyName Boon
    425 schema:givenName Ruben
    426 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0671747777.23
    427 rdf:type schema:Person
    428 sg:person.0704536050.07 schema:affiliation grid-institutes:grid.5596.f
    429 schema:familyName Bird
    430 schema:givenName Matthew
    431 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0704536050.07
    432 rdf:type schema:Person
    433 sg:person.0707254600.80 schema:affiliation grid-institutes:grid.5596.f
    434 schema:familyName Elia
    435 schema:givenName Ilaria
    436 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0707254600.80
    437 rdf:type schema:Person
    438 sg:pub.10.1007/978-1-62703-125-7_17 schema:sameAs https://app.dimensions.ai/details/publication/pub.1005738391
    439 https://doi.org/10.1007/978-1-62703-125-7_17
    440 rdf:type schema:CreativeWork
    441 sg:pub.10.1007/978-1-62703-348-0_11 schema:sameAs https://app.dimensions.ai/details/publication/pub.1011996516
    442 https://doi.org/10.1007/978-1-62703-348-0_11
    443 rdf:type schema:CreativeWork
    444 sg:pub.10.1007/bf02634571 schema:sameAs https://app.dimensions.ai/details/publication/pub.1024847488
    445 https://doi.org/10.1007/bf02634571
    446 rdf:type schema:CreativeWork
    447 sg:pub.10.1007/s00204-016-1745-4 schema:sameAs https://app.dimensions.ai/details/publication/pub.1039080201
    448 https://doi.org/10.1007/s00204-016-1745-4
    449 rdf:type schema:CreativeWork
    450 sg:pub.10.1007/s00204-016-1761-4 schema:sameAs https://app.dimensions.ai/details/publication/pub.1013698897
    451 https://doi.org/10.1007/s00204-016-1761-4
    452 rdf:type schema:CreativeWork
    453 sg:pub.10.1007/s10565-017-9383-z schema:sameAs https://app.dimensions.ai/details/publication/pub.1083400234
    454 https://doi.org/10.1007/s10565-017-9383-z
    455 rdf:type schema:CreativeWork
    456 sg:pub.10.1007/s10911-016-9354-7 schema:sameAs https://app.dimensions.ai/details/publication/pub.1011341548
    457 https://doi.org/10.1007/s10911-016-9354-7
    458 rdf:type schema:CreativeWork
    459 sg:pub.10.1007/s11306-011-0284-5 schema:sameAs https://app.dimensions.ai/details/publication/pub.1051861558
    460 https://doi.org/10.1007/s11306-011-0284-5
    461 rdf:type schema:CreativeWork
    462 sg:pub.10.1038/cr.2012.144 schema:sameAs https://app.dimensions.ai/details/publication/pub.1029165674
    463 https://doi.org/10.1038/cr.2012.144
    464 rdf:type schema:CreativeWork
    465 sg:pub.10.1038/nature06322 schema:sameAs https://app.dimensions.ai/details/publication/pub.1010205458
    466 https://doi.org/10.1038/nature06322
    467 rdf:type schema:CreativeWork
    468 sg:pub.10.1038/nature12271 schema:sameAs https://app.dimensions.ai/details/publication/pub.1034831733
    469 https://doi.org/10.1038/nature12271
    470 rdf:type schema:CreativeWork
    471 sg:pub.10.1038/nbt.2786 schema:sameAs https://app.dimensions.ai/details/publication/pub.1013732820
    472 https://doi.org/10.1038/nbt.2786
    473 rdf:type schema:CreativeWork
    474 sg:pub.10.1038/nbt.3377 schema:sameAs https://app.dimensions.ai/details/publication/pub.1033847015
    475 https://doi.org/10.1038/nbt.3377
    476 rdf:type schema:CreativeWork
    477 sg:pub.10.1038/nbt.4101 schema:sameAs https://app.dimensions.ai/details/publication/pub.1103157300
    478 https://doi.org/10.1038/nbt.4101
    479 rdf:type schema:CreativeWork
    480 sg:pub.10.1038/nbt1361 schema:sameAs https://app.dimensions.ai/details/publication/pub.1045539531
    481 https://doi.org/10.1038/nbt1361
    482 rdf:type schema:CreativeWork
    483 sg:pub.10.1038/ncb3272 schema:sameAs https://app.dimensions.ai/details/publication/pub.1032287924
    484 https://doi.org/10.1038/ncb3272
    485 rdf:type schema:CreativeWork
    486 sg:pub.10.1038/nchembio.364 schema:sameAs https://app.dimensions.ai/details/publication/pub.1020884064
    487 https://doi.org/10.1038/nchembio.364
    488 rdf:type schema:CreativeWork
    489 sg:pub.10.1038/ncomms15267 schema:sameAs https://app.dimensions.ai/details/publication/pub.1085389814
    490 https://doi.org/10.1038/ncomms15267
    491 rdf:type schema:CreativeWork
    492 sg:pub.10.1038/nm815 schema:sameAs https://app.dimensions.ai/details/publication/pub.1016854060
    493 https://doi.org/10.1038/nm815
    494 rdf:type schema:CreativeWork
    495 sg:pub.10.1038/nprot.2015.128 schema:sameAs https://app.dimensions.ai/details/publication/pub.1025360205
    496 https://doi.org/10.1038/nprot.2015.128
    497 rdf:type schema:CreativeWork
    498 sg:pub.10.1038/s42255-019-0054-7 schema:sameAs https://app.dimensions.ai/details/publication/pub.1113305931
    499 https://doi.org/10.1038/s42255-019-0054-7
    500 rdf:type schema:CreativeWork
    501 sg:pub.10.1038/s42255-019-0082-3 schema:sameAs https://app.dimensions.ai/details/publication/pub.1117823480
    502 https://doi.org/10.1038/s42255-019-0082-3
    503 rdf:type schema:CreativeWork
    504 sg:pub.10.1038/s42255-019-0124-x schema:sameAs https://app.dimensions.ai/details/publication/pub.1121787070
    505 https://doi.org/10.1038/s42255-019-0124-x
    506 rdf:type schema:CreativeWork
    507 sg:pub.10.1038/s42255-019-0137-5 schema:sameAs https://app.dimensions.ai/details/publication/pub.1122475460
    508 https://doi.org/10.1038/s42255-019-0137-5
    509 rdf:type schema:CreativeWork
    510 sg:pub.10.1038/sj.onc.1209106 schema:sameAs https://app.dimensions.ai/details/publication/pub.1034184478
    511 https://doi.org/10.1038/sj.onc.1209106
    512 rdf:type schema:CreativeWork
    513 sg:pub.10.1038/srep25187 schema:sameAs https://app.dimensions.ai/details/publication/pub.1028498125
    514 https://doi.org/10.1038/srep25187
    515 rdf:type schema:CreativeWork
    516 sg:pub.10.1186/1471-2105-9-559 schema:sameAs https://app.dimensions.ai/details/publication/pub.1020312314
    517 https://doi.org/10.1186/1471-2105-9-559
    518 rdf:type schema:CreativeWork
    519 sg:pub.10.1186/s13059-020-1934-6 schema:sameAs https://app.dimensions.ai/details/publication/pub.1124677203
    520 https://doi.org/10.1186/s13059-020-1934-6
    521 rdf:type schema:CreativeWork
    522 grid-institutes:grid.11205.37 schema:alternateName 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
    523 schema:name 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
    524 Department of Development and Regeneration, Stem Cell Institute, KU Leuven, Leuven, Belgium
    525 rdf:type schema:Organization
    526 grid-institutes:grid.11486.3a schema:alternateName Laboratory of Angiogenesis and Vascular Metabolism, Center of Cancer Biology, VIB, Leuven, Belgium
    527 schema:name Laboratory of Angiogenesis and Vascular Metabolism, Center of Cancer Biology, VIB, Leuven, Belgium
    528 Laboratory of Angiogenesis and Vascular Metabolism, Department of Oncology, KU Leuven, Leuven, Belgium
    529 rdf:type schema:Organization
    530 grid-institutes:grid.17635.36 schema:alternateName Stem Cell Institute, University of Minnesota, Minneapolis, MN, USA
    531 schema:name Department of Chemical Engineering and Materials Science, University of Minnesota, Minneapolis, MN, USA
    532 Stem Cell Institute, University of Minnesota, Minneapolis, MN, USA
    533 rdf:type schema:Organization
    534 grid-institutes:grid.410569.f schema:alternateName Department of Gastroenterology and Hepatology, UZ Leuven, Leuven, Belgium
    535 schema:name Department of Development and Regeneration, Stem Cell Institute, KU Leuven, Leuven, Belgium
    536 Department of Gastroenterology and Hepatology, UZ Leuven, Leuven, Belgium
    537 Hepatology, Department of Clinical and Experimental Medicine, KU Leuven, Leuven, Belgium
    538 Translational Research in GastroIntestinal Disorders (TARGID), Department of Chronic Diseases, Metabolism and Ageing (CHROMETA), KU Leuven, Leuven, Belgium
    539 rdf:type schema:Organization
    540 grid-institutes:grid.419619.2 schema:alternateName Janssen Research and Development, Beerse, Belgium
    541 schema:name Janssen Research and Development, Beerse, Belgium
    542 rdf:type schema:Organization
    543 grid-institutes:grid.5596.f schema:alternateName Department of Development and Regeneration, Stem Cell Institute, KU Leuven, Leuven, Belgium
    544 Hepatology, Department of Clinical and Experimental Medicine, KU Leuven, Leuven, Belgium
    545 Laboratory of Cellular Metabolism and Metabolic Regulation, Department of Oncology, KU Leuven and Leuven Cancer Institute (LKI), Leuven, Belgium
    546 schema:name Department of Development and Regeneration, Stem Cell Institute, KU Leuven, Leuven, Belgium
    547 Hepatology, Department of Clinical and Experimental Medicine, KU Leuven, Leuven, Belgium
    548 Laboratory of Cellular Metabolism and Metabolic Regulation, Department of Oncology, KU Leuven and Leuven Cancer Institute (LKI), Leuven, Belgium
    549 Laboratory of Cellular Metabolism and Metabolic Regulation, VIB Center for Cancer Biology, VIB, Leuven, Belgium
    550 rdf:type schema:Organization
    551 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
    552 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
    553 rdf:type schema:Organization
     




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


    ...