ArticleNature communications2021
Differential regulation of β-catenin-mediated transcription via N- and C-terminal co-factors governs identity of murine intestinal epithelial stem cells.
Article in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 20 citations in OpenAlex.
- 14-Deoxy-11,12-didehydroandrographolide Promotes Ex Vivo Expansion of Umbilical Cord Blood Stem Cells through Stemness-Related Gene Regulation.ACS omega · 2026Article
- Engineered vesicles facilitate the programmed transdermal-intestinal delivery of cinnabar for insomnia mitigation by modulating serotonin-Htr1d-cAMP.Materials today. Bio · 2025Article
- An evolutionarily conserved role for CTNNB1/β-CATENIN in regulating the development of the corpus callosum.iScience · 2025Article
- Butyrate, IL-4, and EP4 Receptors: A Triad of Colorectal Homeostasis, Protecting Against Onset of Cancer and IBD?BioEssays : news and reviews in molecular, cellular and developmental biology · 2025Review
- Tcf4 regulates secretory cell fate decisions in the small intestine and colon tumors: insights from transcriptomic, histological, and microbiome analyses.Stem cell research & therapy · 2025Article
- Wnt/β-catenin maintains epithelial IL-33 in the colonic stem and progenitor cell niche and drives its induction in colitis.Mucosal immunology · 2025Article
- Intestinal stem cell niche: An upcoming area of immense importance in gastrointestinal disorders.Indian journal of gastroenterology : official journal of the Indian Society of Gastroenterology · 2025Review
- The origin and evolution of Wnt signalling.Nature reviews. Genetics · 2024Review
- Nkd1 functions downstream of Axin2 to attenuate Wnt signaling.Molecular biology of the cell · 2024Article
- Control of Paneth cell function by HuR regulates gut mucosal growth by altering stem cell activity.Life science alliance · 2023Article
- The interactions of Bcl9/Bcl9L with β-catenin and Pygopus promote breast cancer growth, invasion, and metastasis.Oncogene · 2021Article
- WNT as a Driver and Dependency in Cancer.Cancer discovery · 2021Review
Corrections and comments
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Authors and funding
12 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The homeostasis of the gut epithelium relies upon continuous renewal and proliferation of crypt-resident intestinal epithelial stem cells (IESCs). Wnt/β-catenin signaling is required for IESC maintenance, however, it remains unclear how this pathway selectively governs the identity and proliferative decisions of IESCs. Here, we took advantage of knock-in mice harboring transgenic β-catenin alleles with mutations that specifically impair the recruitment of N- or C-terminal transcriptional co-factors. We show that C-terminally-recruited transcriptional co-factors of β-catenin act as all-or-nothing regulators of Wnt-target gene expression. Blocking their interactions with β-catenin rapidly induces loss of IESCs and intestinal homeostasis. Conversely, N-terminally recruited co-factors fine-tune β-catenin's transcriptional output to ensure proper self-renewal and proliferative behaviour of IESCs. Impairment of N-terminal interactions triggers transient hyperproliferation of IESCs, eventually resulting in exhaustion of the self-renewing stem cell pool. IESC mis-differentiation, accompanied by unfolded protein response stress and immune infiltration, results in a process resembling aberrant "villisation" of intestinal crypts. Our data suggest that IESC-specific Wnt/β-catenin output requires selective modulation of gene expression by transcriptional co-factors.
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