p53 promotes revival stem cells in the regenerating intestine after severe radiation injury.
Nat Commun
; 15(1): 3018, 2024 Apr 08.
Article
em En
| MEDLINE
| ID: mdl-38589357
ABSTRACT
Ionizing radiation induces cell death in the gastrointestinal (GI) epithelium by activating p53. However, p53 also prevents animal lethality caused by radiation-induced acute GI syndrome. Through single-cell RNA-sequencing of the irradiated mouse small intestine, we find that p53 target genes are specifically enriched in regenerating epithelial cells that undergo fetal-like reversion, including revival stem cells (revSCs) that promote animal survival after severe damage of the GI tract. Accordingly, in mice with p53 deleted specifically in the GI epithelium, ionizing radiation fails to induce fetal-like revSCs. Using intestinal organoids, we show that transient p53 expression is required for the induction of revival stem cells and is controlled by an Mdm2-mediated negative feedback loop. Together, our findings reveal that p53 suppresses severe radiation-induced GI injury by promoting fetal-like reprogramming of irradiated intestinal epithelial cells.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Lesões por Radiação
/
Proteína Supressora de Tumor p53
Limite:
Animals
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article