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Publication : CREPT is required for murine stem cell maintenance during intestinal regeneration.

First Author  Yang L Year  2021
Journal  Nat Commun Volume  12
Issue  1 Pages  270
PubMed ID  33431892 Mgi Jnum  J:300857
Mgi Id  MGI:6504710 Doi  10.1038/s41467-020-20636-9
Citation  Yang L, et al. (2021) CREPT is required for murine stem cell maintenance during intestinal regeneration. Nat Commun 12(1):270
abstractText  Intestinal stem cells (ISCs) residing in the crypts are critical for the continual self-renewal and rapid recovery of the intestinal epithelium. The regulatory mechanism of ISCs is not fully understood. Here we report that CREPT, a recently identified tumor-promoting protein, is required for the maintenance of murine ISCs. CREPT is preferably expressed in the crypts but not in the villi. Deletion of CREPT in the intestinal epithelium of mice (Vil-CREPT(KO)) results in lower body weight and slow migration of epithelial cells in the intestine. Vil-CREPT(KO) intestine fails to regenerate after X-ray irradiation and dextran sulfate sodium (DSS) treatment. Accordingly, the deletion of CREPT decreases the expression of genes related to the proliferation and differentiation of ISCs and reduces Lgr5(+) cell numbers at homeostasis. We identify that CREPT deficiency downregulates Wnt signaling by impairing beta-catenin accumulation in the nucleus of the crypt cells during regeneration. Our study provides a previously undefined regulator of ISCs.
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