ArticleNature cell biology2022
CRISPR screening uncovers a central requirement for HHEX in pancreatic lineage commitment and plasticity restriction.
Article in Nature cell biology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 37 citations in OpenAlex.
- Understanding development and cellular plasticity in the pancreas in health and disease.Nature reviews. Gastroenterology & hepatology · 2026Review
- Synthetic developmental engineering of human liver organogenesis.Development (Cambridge, England) · 2026Review
- Human pancreatic progenitor organoids define genetic and epigenetic barriers to early PDAC transformation.Developmental cell · 2026Article
- Defective HNF1A hinders GLI3 processing favoring duodenal versus pancreatic fate, thus leading to intestinal elongation in vivo.Genes & development · 2026Article
- Functional chromatin signatures premark future lineage-specific enhancers.Cell genomics · 2026Article
- pertTF: context-aware AI modeling for genome-scale and cross-system perturbation prediction.bioRxiv : the preprint server for biology · 2026Article
- FourC: identifying significant and differential contacts in 1D chromatin conformation data.bioRxiv : the preprint server for biology · 2026Article
- The transcription factor HHEX maintains glucocorticoid levels and protects adrenals from androgen-induced lipid depletion.Nature communications · 2026Article
- Oxidative stress and GPX2 control pancreatic vs. non-pancreatic cell fate in human endoderm.Nature communications · 2026Article
- FOXA2 in cancer: from fundamental biology to clinical translation.Frontiers in oncology · 2026Review
- A stem cell knockout village reveals lineage rewiring and a non-canonical islet cell fate in monogenic diabetes.bioRxiv : the preprint server for biology · 2025Article
- A single-cell transcriptomic dataset of enterocyte-specific HHEX knockdown in the Drosophila larval midgut.Scientific data · 2025Article
- Bridging pancreatic and hepatic development: overlapping genes and their role in diabetes.Cellular & molecular biology letters · 2025Review
- Systematic identification and characterization of regulators of aryl hydrocarbon receptor signaling.bioRxiv : the preprint server for biology · 2025Article
- Perturbomics: CRISPR-Cas screening-based functional genomics approach for drug target discovery.Experimental & molecular medicine · 2025Review
- Decoding heterogeneous single-cell perturbation responses.Nature cell biology · 2025Article
- Article
- Unraveling the future of genomics: CRISPR, single-cell omics, and the applications in cancer and immunology.Frontiers in genome editing · 2025Review
- Parallel genome-scale CRISPR-Cas9 screens uncouple human pluripotent stem cell identity versus fitness.Nature communications · 2024Article
- CRISPR screening uncovers a long-range enhancer for ONECUT1 in pancreatic differentiation and links a diabetes risk variant.Cell reports · 2024Article
Corrections and comments
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Authors and funding
25 authors at 5 institutions in 1 country.
Funding
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.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.