Key mechanisms to improve intestinal regeneration and alleviate the side effects of radiotherapy discovered CNIO_Cancer JExpMed
Intestinal epithelium regenerates rapidly through proliferation of intestinal stem cells , orchestrated by potent mitogens secreted within the crypt niche. However, mechanisms regulating these mitogenic factors remain largely unknown. Here, we demonstrate that transit-amplifying cells, marked by unconventional prefoldin RPB5 interactor , control R-spondin production to guide ISC proliferation.
R-spondin supplementation or restoration of R-spondin levels via cell death inhibition by c-MYC elimination or the suppression of inflammation reinstates ISC proliferation in URI-depleted mice. However, selective c-MYC and p53 suppression are required to fully restore TA cell survival and differentiation capacity and preserve complete intestinal architecture.
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