The DOI matches its Crossref record; 70 of the 70 references it cites were found in a registry or an index.
BMP restricts stemness of intestinal Lgr5(+) stem cells by directly suppressing their signature genes
Open accessAbstract
The intestinal epithelium possesses a remarkable self-renewal ability, which is mediated by actively proliferating Lgr5 + stem cells. Bone morphogenetic protein (BMP) signalling represents one major counterforce that limits the hyperproliferation of intestinal epithelium, but the exact mechanism remains elusive. Here we demonstrate that epithelial BMP signalling plays an indispensable role in restricting Lgr5 + stem cell expansion to maintain intestinal homeostasis and prevent premalignant hyperproliferation on damage. Mechanistically, BMP inhibits stemness of Lgr5 + stem cells through Smad-mediated transcriptional repression of a large number of stem cell signature genes, including Lgr5 , and this effect is independent of Wnt/β-catenin signalling. Smad1/Smad4 recruits histone deacetylase HDAC1 to the promoters to repress transcription, and knockout of Smad4 abolishes the negative effects of BMP on stem cells. Our findings therefore demonstrate that epithelial BMP constrains the Lgr5 + stem cell self-renewal via Smad-mediated repression of stem cell signature genes to ensure proper homeostatic renewal of intestinal epithelium.
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“Although SMAD1 has been shown to regulate intestinal homeostasis by constraining Lgr5+ stem cell expansion,52 its role in treatment-induced lineage plasticity remains under-explored.”
From Paneth-like transition drives resistance to dual targeting of KRAS and EGFR in colorectal cancer (2026) · cites this paper as [52]
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“As a major receptor-activated SMADs (R-SMADs) downstream of BMP pathway, SMAD1 has been reported to repress Lgr5+ stem cell signature genes, thereby limiting stem cell expansion and maintaining intestinal homeostasis.50–52”
From Paneth-like transition drives resistance to dual targeting of KRAS and EGFR in colorectal cancer (2026) · cites this paper as [52]
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Cites
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Single Lgr5 stem cells build crypt-villus structures in vitro without a mesenchymal niche
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Development of an in-vitro intestinal model featuring peristaltic motion
Gérémie, L. (2019) · theses.fr (ABES) · doi:10.70675/c3a13b73z70d7z4143zbb1eza871bcd89028
Rispal, J. (2020) · theses.fr (ABES) · doi:10.70675/4a1dc94dzc25bz4007z952cz1d4dccdde1e8
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Single-Cell Transcriptome Profiles of Foxl1-Lineage Cells Along the Intestinal Crypt–Villus Axis
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Self-citationBechard, M. E., Chen, Z., Zhao, P., Aramandla, R., Yang, Y., Simmons, A. J., Washington, M. K., Franklin, J. L., Lau, K. S., & Coffey, R. J. (2026) · Cellular and Molecular Gastroenterology and Hepatology · doi:10.1016/j.jcmgh.2026.101873
Intestinal stem cells in radiation-induced intestinal injury: mechanisms and therapeutic targets
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Self-citationReddy, P. R., Ikeda, T., Yamamoto, A., Leach, T., McCord, K., Xu, L., Wu, M.-C., Sumii, Y., Bodhale, N., Kambara, Y., et al. (2026) · Research Square · doi:10.21203/rs.3.rs-11143774/v1
Metadata
- Authors
- Qi, Z., Li, Y., Zhao, B., Xu, C., Liu, Y., Li, H., Zhang, B., Wang, X., Yang, X., Xie, W., Li, B., Han, J.-D. J., & Chen, Y.-G.
- Affiliations
- Center for Life Sciences (CN)
- Chinese Academy of Sciences (CN)
- Tsinghua University (CN)
- State Key Laboratory of Proteomics (CN)
- Shanghai Jiao Tong University (CN)
- Corresponding author
- Chen, Ye-Guang
- ORCID
- Venue
- Nature Communications
- Published
- 2017-01-06
- Volume
- 8
- Issue
- 1
- Pages
- 13824-13824
- ISSN
- 2041-1723 (ISSN-L)
- PMC
- PMC5227110
- OpenAlex
- W2567946031
- Cited by
- 320
- References
- 70
- Citations by year
- 2026: 18 · 2025: 35 · 2024: 41 · 2023: 39 · 2022: 41 · 2021: 46 · 2020: 42 · 2019: 24 · 2018: 26 · 2017: 8
- FWCI
- 11.17
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Nature Communications (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Natural Science Foundation of China (973 Program, 31330049, 91519310)
- National Key Research and Development Program of China (31330049, 2013CB933700)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › TGF-β signaling in diseases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Wnt/β-catenin signaling in development and cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Keywords
- BMP signaling, Lgr5+ stem cells, intestinal stem cells, stem cell self-renewal, HDAC1, transcriptional repression, intestinal homeostasis, epithelial hyperproliferation, intestinal epithelium
- MeSH terms
- Cell Self Renewal, Animals, Female, Gene Expression Regulation, Histone Deacetylases, Homeostasis, Intestines, Male, Mice, Inbred C57BL, Precancerous Conditions, Promoter Regions, Genetic, Protein Binding, Radiation, Ionizing, Regeneration, Stem Cells, Transcription, Genetic, Bone Morphogenetic Proteins, Gene Expression Profiling, Receptors, G-Protein-Coupled, Cell Proliferation, Wnt Proteins, beta Catenin, Smad Proteins, Cell Cycle Checkpoints, Wnt Signaling Pathway
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