ArticleCell death and differentiation2015
Ribosome biogenesis dysfunction leads to p53-mediated apoptosis and goblet cell differentiation of mouse intestinal stem/progenitor cells.
Article in Cell death and differentiation, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 39 citations in OpenAlex.
- SLC4A9 deficiency is involved in Sjögren's syndrome and enamel defects through RPS27-triggered ribosomal stress.Experimental & molecular medicine · 2026Article
- DCAF13 Safeguards Hematopoietic Stem Cells via RRS1-Regulated Ribosome Biogenesis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Emerging roles of ribosome translation in stem cells and stem cell therapy - a review.Cell & bioscience · 2025Review
- Molecular mechanisms underlying the effects of hypo- and hyper-prolactinemia on spermatogenesis and fertility in male rats.Journal of endocrinological investigation · 2025Article
- Repurposing colforsin daropate to treat MYC-driven high-grade serous ovarian carcinomas.Science signaling · 2024Article
- Extracorporeal photopheresis as a promising strategy for the treatment of graft-versus-host disease after CAR T-cell therapy.Blood advances · 2024Article
- Decoding Ribosome Heterogeneity: A New Horizon in Cancer Therapy.Biomedicines · 2024Review
- Ribosome profiling analysis reveals the roles of DDX41 in translational regulation.International journal of hematology · 2023Article
- The homeostatic regulation of ribosome biogenesis.Seminars in cell & developmental biology · 2023Review
- Nuclear α-Synuclein-Derived Cytotoxic Effect via Altered Ribosomal RNA Processing in Primary Mouse Embryonic Fibroblasts.International journal of molecular sciences · 2023Article
- Differential gene expression in iPSC-derived human intestinal epithelial cell layers following exposure to two concentrations of butyrate, propionate and acetate.Scientific reports · 2022Article
- Ribosome impairment regulates intestinal stem cell identity via ZAKɑ activation.Nature communications · 2022Article
- Integration of human inspection and artificial intelligence-based morphological typing of patient-derived organoids reveals interpatient heterogeneity of colorectal cancer.Cancer science · 2022Article
- mRNA Translation Is Dynamically Regulated to Instruct Stem Cell Fate.Frontiers in molecular biosciences · 2022Review
- Translational control of stem cell function.Nature reviews. Molecular cell biology · 2021Review
- The HSP90/R2TP assembly chaperone promotes cell proliferation in the intestinal epithelium.Nature communications · 2021Article
- Identification of Hub Genes in Different Stages of Colorectal Cancer through an Integrated Bioinformatics Approach.International journal of environmental research and public health · 2021Article
- Requirement of Bccip for the Regeneration of Intestinal Progenitors.The American journal of pathology · 2021Article
- Review
- Compensation between Wnt-driven tumorigenesis and cellular responses to ribosome biogenesis inhibition in the murine intestinal epithelium.Cell death and differentiation · 2020Article
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Ribosome biogenesis is an essential cellular process. Its impairment is associated with developmental defects and increased risk of cancer. The in vivo cellular responses to defective ribosome biogenesis and the underlying molecular mechanisms are still incompletely understood. In particular, the consequences of impaired ribosome biogenesis within the intestinal epithelium in mammals have not been investigated so far. Here we adopted a genetic approach to investigate the role of Notchless (NLE), an essential actor of ribosome biogenesis, in the adult mouse intestinal lineage. Nle deficiency led to defects in the synthesis of large ribosomal subunit in crypts cells and resulted in the rapid elimination of intestinal stem cells and progenitors through distinct types of cellular responses, including apoptosis, cell cycle arrest and biased differentiation toward the goblet cell lineage. Similar observations were made using the rRNA transcription inhibitor CX-5461 on intestinal organoids culture. Importantly, we found that p53 activation was responsible for most of the cellular responses observed, including differentiation toward the goblet cell lineage. Moreover, we identify the goblet cell-specific marker Muc2 as a direct transcriptional target of p53. Nle-deficient ISCs and progenitors disappearance persisted in the absence of p53, underlying the existence of p53-independent cellular responses following defective ribosome biogenesis. Our data indicate that NLE is a crucial factor for intestinal homeostasis and provide new insights into how perturbations of ribosome biogenesis impact on cell fate decisions within the intestinal epithelium.
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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.