Intestinal stem cell aging at single-cell resolution: Transcriptional perturbations alter cell developmental trajectory reversed by gerotherapeutics.

ABSTRACT: The intestinal epithelium consists of cells derived from continuously cycling Lgr5^hi intestinal stem cells (Lgr5^hi ISCs) that mature developmentally in an ordered fashion as the cells progress along the crypt-luminal axis. Perturbed function of Lgr5^hi ISCs with aging is documented, but the consequent impact on overall mucosal homeostasis has not been defined. Using single-cell RNA sequencing, the progressive maturation of progeny was dissected in the mouse intestine, which revealed that transcriptional reprogramming with aging in Lgr5^hi ISCs retarded the maturation of cells in their progression along the crypt-luminal axis. Importantly, treatment with metformin or rapamycin at a late stage of mouse lifespan reversed the effects of aging on the fu

SUBMITTER: Choi J 

PROVIDER: S-EPMC10186593 | biostudies-literature | 2023 May

REPOSITORIES: biostudies-literature