| Autor: |
Creff, Justine, Nowosad, Ada, Prel, Anne, Pizzoccaro, Anne, Aguirrebengoa, Marion, Duquesnes, Nicolas, Callot, Caroline, Jungas, Thomas, Dozier, Christine, Besson, Arnaud |
| Zdroj: |
Cell Reports; June 2023, Vol. 42 Issue: 6 |
| Abstrakt: |
p57Kip2is a cyclin/CDK inhibitor and a negative regulator of cell proliferation. Here, we report that p57 regulates intestinal stem cell (ISC) fate and proliferation in a CDK-independent manner during intestinal development. In the absence of p57, intestinal crypts exhibit an increased proliferation and an amplification of transit-amplifying cells and of Hopx+ISCs, which are no longer quiescent, while Lgr5+ISCs are unaffected. RNA sequencing (RNA-seq) analyses of Hopx+ISCs show major gene expression changes in the absence of p57. We found that p57 binds to and inhibits the activity of Ascl2, a transcription factor critical for ISC specification and maintenance, by participating in the recruitment of a corepressor complex to Ascl2 target gene promoters. Thus, our data suggest that, during intestinal development, p57 plays a key role in maintaining Hopx+ISC quiescence and repressing the ISC phenotype outside of the crypt bottom by inhibiting the transcription factor Ascl2 in a CDK-independent manner. |
| Databáze: |
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