ArticleProceedings of the National Academy of Sciences of the United States of America2021
High Yap and Mll1 promote a persistent regenerative cell state induced by Notch signaling and loss of p53.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 29 citations in OpenAlex.
- Downregulation of MLL1 Promotes Intestinal Epithelial Barrier Repair Through Gata4/Bmp4 Activation to Ameliorate Crohn's Disease-Like Colitis in Mice.Cell proliferation · 2026Article
- Article
- On the mechanisms of epidermal stemness and differentiation.NPJ systems biology and applications · 2025Article
- Extrusion of BMP2+ surface colonocytes promotes stromal remodeling and tissue regeneration.Nature communications · 2025Article
- Molecular Pathways Implicated in the Differentiation and Function of Epididymal Basal Cells.Advances in experimental medicine and biology · 2025Review
- Hippo/YAP signaling pathway in colorectal cancer: regulatory mechanisms and potential drug exploration.Frontiers in oncology · 2025Review
- Mechanism and application of feedback loops formed by mechanotransduction and histone modifications.Genes & diseases · 2024Review
- Activation of fetal-like molecular programs during regeneration in the intestine and beyond.Cell stem cell · 2024Review
- Cellular memory function from 3D to 2D: Three-dimensional high density collagen microfiber cultures induce their resistance to reactive oxygen species.Materials today. Bio · 2024Article
- Epigenetic drug screening for trophoblast syncytialization reveals a novel role for MLL1 in regulating fetoplacental growth.BMC medicine · 2024Article
- Gastrointestinal tract organoids as novel tools in drug discovery.Frontiers in pharmacology · 2024Review
- Hippo Signaling Pathway in Colorectal Cancer: Modulation by Various Signals and Therapeutic Potential.Analytical cellular pathology (Amsterdam) · 2024Review
- MicroRNA-200 Loaded Lipid Nanoparticles Promote Intestinal Epithelium Regeneration in Canonical MicroRNA-Deficient Mice.ACS nano · 2023Article
- IL-38 regulates intestinal stem cell homeostasis by inducing WNT signaling and beneficial IL-1β secretion.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Pharmacological inhibition of the mixed lineage leukemia 1-menin interaction aggravates acute kidney injury induced by folic acid and ischemia-reperfusion in mice.American journal of physiology. Renal physiology · 2023Article
- Loss of p53 enhances the tumor-initiating potential and drug resistance of clonogenic multiple myeloma cells.Blood advances · 2023Article
- Establishment of gastrointestinal assembloids to study the interplay between epithelial crypts and their mesenchymal niche.Nature communications · 2023Article
- YAP/TAZ as master regulators in cancer: modulation, function and therapeutic approaches.Nature cancer · 2023Review
- Organoids as a Model System for Studying Notch Signaling in Intestinal Epithelial Homeostasis and Intestinal Cancer.The American journal of pathology · 2022Review
- Epigenetic modifier balances Mapk and Wnt signalling in differentiation of goblet and Paneth cells.Life science alliance · 2022Article
Corrections and comments
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Authors and funding
16 authors at 8 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Specified intestinal epithelial cells reprogram and contribute to the regeneration and renewal of the epithelium upon injury. Mutations that deregulate such renewal processes may contribute to tumorigenesis. Using intestinal organoids, we show that concomitant activation of Notch signaling and ablation of p53 induce a highly proliferative and regenerative cell state, which is associated with increased levels of Yap and the histone methyltransferase Mll1. The induced signaling system orchestrates high proliferation, self-renewal, and niche-factor-independent growth, and elevates the trimethylation of histone 3 at lysine 4 (H3K4me3). We demonstrate that Yap and Mll1 are also elevated in patient-derived colorectal cancer (CRC) organoids and control growth and viability. Our data suggest that Notch activation and p53 ablation induce a signaling circuitry involving Yap and the epigenetic regulator Mll1, which locks cells in a proliferative and regenerative state that renders them susceptible for tumorigenesis.
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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.