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BMP suppresses Wnt signaling via the Bcl11b-regulated NuRD complex to maintain intestinal stem cells.

Author information

Affiliations

  • 1. The State Key Laboratory of Membrane Biology, Tsinghua-Peking Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing, 100084, China.
      Authors
    • Li Y 1
    • Wang X 1
    • Huang M 1
    • Li C 1
    • Tang Y 1
    • Song W 1
    • Liu Y 1
    • Chen YG 1, 2
    (8 authors)
  • 2. Guangzhou National Laboratory, Guangzhou, 510700, China.
      Authors
    • Wang X 2
    • Li S 2
    • Yu S 2
    • Wang Y 2
    • Chen YG 1, 2
    (5 authors)
  • 3. MOE Key Laboratory of Protein Sciences, School of Life Sciences, Tsinghua University, Beijing, 100084, China.
      Authors
    • Wu W 3
    (1 author)

ORCIDs linked to this article

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The EMBO Journal, 21 Oct 2024,
https://doi.org/10.1038/s44318-024-00276-1 PMID: 39433900 

Abstract 

Lgr5+ intestinal stem cells (ISCs) are crucial for the intestinal epithelium renewal and regeneration after injury. However, the mechanism underlying the interplay between Wnt and BMP signaling in this process is not fully understood. Here we report that Bcl11b, which is downregulated by BMP signaling, enhances Wnt signaling to maintain Lgr5+ ISCs and thus promotes the regeneration of the intestinal epithelium upon injury. Loss of Bcl11b function leads to a significant decrease of Lgr5+ ISCs in both intestinal crypts and cultured organoids. Mechanistically, BMP suppresses the expression of Bcl11b, which can positively regulate Wnt target genes by inhibiting the function of the Nucleosome Remodeling and Deacetylase (NuRD) complex and facilitating the β-catenin-TCF4 interaction. Bcl11b can also promote intestinal epithelium repair after injuries elicited by both irradiation and DSS-induced inflammation. Furthermore, Bcl11b deletion prevents proliferation and tumorigenesis of colorectal cancer cells. Together, our findings suggest that BMP suppresses Wnt signaling via Bcl11b regulation, thus balancing homeostasis and regeneration in the intestinal epithelium.

Full text links 

Read article at publisher's site: https://doi.org/10.1038/s44318-024-00276-1

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Funding 

Funders who supported this work.

MOST | National Key Research and Development Program of China (NKPs) (1)

MOST | National Natural Science Foundation of China (NSFC) (2)

Shenzhen Medical Research Fund (1)

| Beijing Science and Technology Planning Project (Beijing Science and Technology Plan Project) (1)

| Natural Science Foundation of Jiangxi Province (Jiangxi Natural Science Foundation) (1)