Fall of Parp3 restrains Lgr5+ stem cells proliferation and mucosal renovation in intestinal aging

Abstract Background The aging small intestine has a great impact on body health. One of the obvious characteristics is the degeneration of epithelium turnover. The acknowledged Lgr5+ intestinal stem cell is the key factor. Methods We used Lgr5-EGFP transgenic mice in three different ages (young group:3-6 months, middle group:12-14 months and old group:22-24 months) to mark the Lgr5+ISCs. We collected the jejunum for histology, immunofluorescence, western-blotting and PCR, we isolated the crypts for organoid culture and sorted out the Lgr5hi cells for bulk RNA sequence. Results In tissue, the crypts depth, proliferating cells and Lgr5+ISCs number increased in middle group (12-14 months) and then decreased in old group (22-24 months). The number of proliferating Lgr5+ISCs gradually decreased from young to old. In organoids, the buddings number and projected area, Lgr5+ISCs ratio also decreased from young to old. Both gene expression of Parp3 and protein level of Parp3 increased in middle and old group. Parp3 inhibitors slowed down organoids’ growth of the middle age. Conclusion Parp3 might participate in regulating the proliferation capacity of Lgr5+ISCs during aging.