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

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-caten

SUBMITTER: Li Y 

PROVIDER: S-EPMC11612440 | biostudies-literature | 2024 Dec

REPOSITORIES: biostudies-literature