CREPT is required for murine stem cell maintenance during intestinal regeneration.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 33431892.
- Also identified by DOI 10.1038/s41467-020-20636-9 and PMC identifier 7801528.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
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<sup>KO</sup>) results in lower body weight and slow migration of epithelial cells in the intestine. Vil-CREPT<sup>KO</sup> 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<sup>+</sup> cell numbers at homeostasis. We identify that CREPT deficiency downregulates Wnt signaling by impairing β-catenin accumulation in the nucleus of the crypt cells during regeneration. Our study provides a previously undefined regulator of ISCs.
Medical subject headings
- Cell Cycle Proteins
- Intestines
- Neoplasm Proteins
- Regeneration
- Stem Cells