ArticleNature genetics2019
Genome-scale screens identify JNK-JUN signaling as a barrier for pluripotency exit and endoderm differentiation.
Article in Nature genetics, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 83 papers, 2 of them syntheses that pooled it.
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Who cites it
83 citing papers in PubMed, 2 syntheses or guidelines pooled it, 141 citations in OpenAlex.
- Development and trend of stem cell therapy for diabetes: a comprehensive review based on knowledge visualization.Frontiers in immunology · 2026Pooled it
- Molecular Mechanisms Underlying Pluripotency and Self-Renewal of Embryonic Stem Cells.International journal of molecular sciences · 2023Pooled it
- A Comprehensive Review on CRISPR-Based Screening and Its Applications.Molecular biotechnology · 2026Review
- DDX5 (p68) and UbE2T as emerging superior cancer therapeutic targets: dual molecular glue target degradation by FL118 for conquering difficult-to-treat cancers.Journal of experimental & clinical cancer research : CR · 2026Review
- Functional chromatin signatures premark future lineage-specific enhancers.Cell genomics · 2026Article
- Intermolecular 3'UTR-3'UTR interactions drive Wnt gene activation through heteromeric protein assembly.bioRxiv : the preprint server for biology · 2026Article
- Bioengineering Pancreatic Organoids and iPSC-Derived β-Cells for Diabetes: Materials, Devices, and Translational Challenges.Bioengineering (Basel, Switzerland) · 2026Review
- Depolymerizing F-actin accelerates the exit from pluripotency to enhance stem cell-derived islet differentiation.Nature communications · 2026Article
- Advances in Internal Organogenesis: Differentiation and Morphogenesis of Human Ventral Cavity Organs.Stem cell reviews and reports · 2026Review
- Identification and validation of ferroptosis-related key hub genes linking hypoxia and osteoporosis.BMC musculoskeletal disorders · 2025Article
- BACH1 recruits STAT3 to enhance leukemia inhibitory factor receptor activity and augments the self-renewal capacity of mouse embryonic stem cells.Stem cell research & therapy · 2025Article
- Mitochondrial dysfunction by glyoxalase 1 deficiency disrupts definitive endoderm and alveolar development of human pluripotent stem cells.Experimental & molecular medicine · 2025Article
- Genome-wide CRISPR screen identifies Menin and SUZ12 as regulators of human developmental timing.Nature cell biology · 2025Article
- Discovery of NANOG enhancers and their essential roles in self-renewal and differentiation in human embryonic stem cells.Stem cell reports · 2025Article
- A spatiotemporal and machine-learning platform facilitates the manufacturing of hPSC-derived esophageal mucosa.Developmental cell · 2025Article
- Decoding heterogeneous single-cell perturbation responses.Nature cell biology · 2025Article
- Pioneer factor GATA6 promotes colorectal cancer through 3D genome regulation.Science advances · 2025Article
- c-JUN: a chromatin repressor that limits mesoderm differentiation in human pluripotent stem cells.Nucleic acids research · 2025Article
- Chemically defined and growth factor-free system for highly efficient endoderm induction of human pluripotent stem cells.Stem cell reports · 2025Article
- Parallel genome-scale CRISPR-Cas9 screens uncouple human pluripotent stem cell identity versus fitness.Nature communications · 2024Article
23 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
24 authors at 5 institutions in 2 countries.
Funding
Abstract
Human embryonic stem cells (ESCs) and human induced pluripotent stem cells hold great promise for cell-based therapies and drug discovery. However, homogeneous differentiation remains a major challenge, highlighting the need for understanding developmental mechanisms. We performed genome-scale CRISPR screens to uncover regulators of definitive endoderm (DE) differentiation, which unexpectedly uncovered five Jun N-terminal kinase (JNK)-JUN family genes as key barriers of DE differentiation. The JNK-JUN pathway does not act through directly inhibiting the DE enhancers. Instead, JUN co-occupies ESC enhancers with OCT4, NANOG, SMAD2 and SMAD3, and specifically inhibits the exit from the pluripotent state by impeding the decommissioning of ESC enhancers and inhibiting the reconfiguration of SMAD2 and SMAD3 chromatin binding from ESC to DE enhancers. Therefore, the JNK-JUN pathway safeguards pluripotency from precocious DE differentiation. Direct pharmacological inhibition of JNK significantly improves the efficiencies of generating DE and DE-derived pancreatic and lung progenitor cells, highlighting the potential of harnessing the knowledge from developmental studies for regenerative medicine.
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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.