p53 promotes revival stem cells in the regenerating intestine after severe radiation injury
p53 promotes revival stem cells in the regenerating intestine after severe radiation injury
Abstract Ionizing radiation induces cell death in the gastrointestinal (GI) epithelium by activating p53. However, p53 also prevents animal lethality caused by radiation-induced GI injury. Through single-cell RNA-sequencing of the irradiated mouse intestine, we find that p53 target genes are specifically enriched in stem cells of the regenerating epithelium, including revival stem cells that promote animal survival after GI damage. Accordingly, in mice with p53 deleted specifically in the GI epithelium, ionizing radiation fails to induce revival stem cells. Using intestinal organoids, we show that transient p53 expression is required for the induction of revival stem cells that is controlled by an Mdm2-mediated negative feedback loop. These results suggest that p53 suppresses severe radiation-indued GI injury by promoting intestinal epithelial cell reprogramming. One-Sentence SummaryAfter severe radiation injury to the intestine, transient p53 activity induces revival stem cells to promote regeneration.
Koumenis Costas、Kuo Hsuan-Cheng、Fink Mardi、Burner Danielle N.、Satow Sloane、Hasapis Stephanie、Luo Lixia、Ma Yan、Kirsch David G.、Attardi Laura D.、Lee Chang-Lung、Verginadis Ioannis、Minn Andy J、Ghinnagow Reem、Ayyaz Arshad、Daniel Andrea R.、Morral Clara、Wrana Jeffrey L.、Driver Lucy M.
基础医学分子生物学细胞生物学
Koumenis Costas,Kuo Hsuan-Cheng,Fink Mardi,Burner Danielle N.,Satow Sloane,Hasapis Stephanie,Luo Lixia,Ma Yan,Kirsch David G.,Attardi Laura D.,Lee Chang-Lung,Verginadis Ioannis,Minn Andy J,Ghinnagow Reem,Ayyaz Arshad,Daniel Andrea R.,Morral Clara,Wrana Jeffrey L.,Driver Lucy M..p53 promotes revival stem cells in the regenerating intestine after severe radiation injury[EB/OL].(2025-03-28)[2025-07-21].https://www.biorxiv.org/content/10.1101/2023.04.27.538576.点此复制
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