CRISPR screening uncovers a central requirement for HHEX in pancreatic lineage commitment and plasticity restriction View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2022-07-04

AUTHORS

Dapeng Yang, Hyunwoo Cho, Zakieh Tayyebi, Abhijit Shukla, Renhe Luo, Gary Dixon, Valeria Ursu, Stephanie Stransky, Daniel M. Tremmel, Sara D. Sackett, Richard Koche, Samuel J. Kaplan, Qing V. Li, Jiwoon Park, Zengrong Zhu, Bess P. Rosen, Julian Pulecio, Zhong-Dong Shi, Yaron Bram, Robert E. Schwartz, Jon S. Odorico, Simone Sidoli, Christopher V. Wright, Christina S. Leslie, Danwei Huangfu

ABSTRACT

The pancreas and liver arise from a common pool of progenitors. However, the underlying mechanisms that drive their lineage diversification from the foregut endoderm are not fully understood. To tackle this question, we undertook a multifactorial approach that integrated human pluripotent-stem-cell-guided differentiation, genome-scale CRISPR–Cas9 screening, single-cell analysis, genomics and proteomics. We discovered that HHEX, a transcription factor (TF) widely recognized as a key regulator of liver development, acts as a gatekeeper of pancreatic lineage specification. HHEX deletion impaired pancreatic commitment and unleashed an unexpected degree of cellular plasticity towards the liver and duodenum fates. Mechanistically, HHEX cooperates with the pioneer TFs FOXA1, FOXA2 and GATA4, shared by both pancreas and liver differentiation programmes, to promote pancreas commitment, and this cooperation restrains the shared TFs from activating alternative lineages. These findings provide a generalizable model for how gatekeeper TFs like HHEX orchestrate lineage commitment and plasticity restriction in broad developmental contexts. More... »

PAGES

1064-1076

References to SciGraph publications

  • 2008-09-17. Model-based Analysis of ChIP-Seq (MACS) in GENOME BIOLOGY
  • 2017-01-16. Massively parallel digital transcriptional profiling of single cells in NATURE COMMUNICATIONS
  • 2014-12-05. MAGeCK enables robust identification of essential genes from genome-scale CRISPR/Cas9 knockout screens in GENOME BIOLOGY
  • 2019-05-20. Genome-scale screens identify JNK–JUN signaling as a barrier for pluripotency exit and endoderm differentiation in NATURE GENETICS
  • 2014-03-23. Use Model-Based Analysis of ChIP-Seq (MACS) to Analyze Short Reads Generated by Sequencing Protein–DNA Interactions in Embryonic Stem Cells in STEM CELL TRANSCRIPTIONAL NETWORKS
  • 2021-08-25. Quantitative lineage analysis identifies a hepato-pancreato-biliary progenitor niche in NATURE
  • 1994-10. Insulin-promoter-factor 1 is required for pancreas development in mice in NATURE
  • 2014-12-05. Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2 in GENOME BIOLOGY
  • 2006-11-05. BMP-4 is required for hepatic specification of mouse embryonic stem cell–derived definitive endoderm in NATURE BIOTECHNOLOGY
  • 2014-09-11. Reversal of diabetes with insulin-producing cells derived in vitro from human pluripotent stem cells in NATURE BIOTECHNOLOGY
  • 2005-06. The initiation of liver development is dependent on Foxa transcription factors in NATURE
  • 1997-01. Pancreatic agenesis attributable to a single nucleotide deletion in the human IPF1 gene coding sequence in NATURE GENETICS
  • 2010-12-03. ΔNp63 is an ectodermal gatekeeper of epidermal morphogenesis in CELL DEATH & DIFFERENTIATION
  • 2014-07-30. Improved vectors and genome-wide libraries for CRISPR screening in NATURE METHODS
  • 2021-11-17. Sequence logic at enhancers governs a dual mechanism of endodermal organ fate induction by FOXA pioneer factors in NATURE COMMUNICATIONS
  • 2007-04-23. Development of the mammalian liver and ventral pancreas is dependent on GATA4 in BMC DEVELOPMENTAL BIOLOGY
  • 2017-04-05. Myt1l safeguards neuronal identity by actively repressing many non-neuronal fates in NATURE
  • 2019-03-21. Characterization of cell fate probabilities in single-cell data with Palantir in NATURE BIOTECHNOLOGY
  • 2013-10-06. Transposition of native chromatin for fast and sensitive epigenomic profiling of open chromatin, DNA-binding proteins and nucleosome position in NATURE METHODS
  • 2015-12-10. MAST: a flexible statistical framework for assessing transcriptional changes and characterizing heterogeneity in single-cell RNA sequencing data in GENOME BIOLOGY
  • 2020-08-27. Single cell transcriptomics identifies a signaling network coordinating endoderm and mesoderm diversification during foregut organogenesis in NATURE COMMUNICATIONS
  • 2016-01-18. Optimized sgRNA design to maximize activity and minimize off-target effects of CRISPR-Cas9 in NATURE BIOTECHNOLOGY
  • 2020-02-24. Targeting the cytoskeleton to direct pancreatic differentiation of human pluripotent stem cells in NATURE BIOTECHNOLOGY
  • Journal

    TITLE

    Nature Cell Biology

    ISSUE

    7

    VOLUME

    24

    Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/s41556-022-00946-4

    DOI

    http://dx.doi.org/10.1038/s41556-022-00946-4

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1149203125

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/35787684


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