平衡
肠上皮
蛋白质精氨酸甲基转移酶5
上皮
干细胞
细胞生物学
细胞生长
祖细胞
肠粘膜
类有机物
潘尼斯电池
生物
甲基转移酶
小肠
内科学
内分泌学
甲基化
遗传学
基因
医学
作者
Leilei Li,Zhe Zhang,Xu Wang,Huaijuan Zhao,Liansheng Liu,Yanhui Xiao,Shan Hua,Ye‐Guang Chen
出处
期刊:Advanced Science
[Wiley]
日期:2025-02-03
卷期号:12 (12): e2415559-e2415559
被引量:1
标识
DOI:10.1002/advs.202415559
摘要
Intestinal homeostasis is sustained by self-renewal of intestinal stem cells, which continuously divide and produce proliferative transit-amplifying (TA) and progenitor cells. Protein arginine methyltransferases 5 (PRMT5) plays a crucial role in regulating homeostasis of various mammalian tissues. However, its function in intestinal homeostasis remains elusive. In this study, conditional knockout of Prmt5 in the mouse intestinal epithelium leads to a reduction in stem cell population, suppression of cell proliferation, and increased cell apoptosis within the intestinal crypts, accompanied with shortened gut length, decreased mouse body weight, and eventual animal mortality. Additionally, Prmt5 deletion or its enzymatic inhibition in intestinal organoids in vitro also shows resembling cellular phenotypes. Methylome profiling identifies 90 potential Prmt5 substrates, which are involved in RNA-related biological processes and cell division. Consistently, Prmt5 depletion in intestinal organoids leads to aberrant alternative splicing in a subset of genes related to the mitotic cell cycle. Furthermore, Prmt5 loss triggers p53-mediated apoptosis in the intestinal epithelium. Collectively, the findings uncover an indispensable role of PRMT5 in promoting cell proliferation and survival, as well as maintaining stem cells in the gut epithelium.
科研通智能强力驱动
Strongly Powered by AbleSci AI