Notch signaling modulates proliferation and differentiation of intestinal crypt base columnar stem cells.

ABSTRACT: Notch signaling is known to regulate the proliferation and differentiation of intestinal stem and progenitor cells; however, direct cellular targets and specific functions of Notch signals had not been identified. We show here in mice that Notch directly targets the crypt base columnar (CBC) cell to maintain stem cell activity. Notch inhibition induced rapid CBC cell loss, with reduced proliferation, apoptotic cell death and reduced efficiency of organoid initiation. Furthermore, expression of the CBC stem cell-specific marker Olfm4 was directly dependent on Notch signaling, with transcription activated through RBP-Jκ binding sites in the promoter. Notch inhibition also led to precocious differentiation of epithelial progenitors into secretory cell types, including large numbers of cells t

SUBMITTER: VanDussen KL 

PROVIDER: S-EPMC3252352 | biostudies-literature | 2012 Feb

REPOSITORIES: biostudies-literature