LGR5型
干细胞
Wnt信号通路
肠上皮
细胞生物学
再生(生物学)
地穴
生物
上皮
平衡
细胞生长
信号转导
癌症干细胞
内分泌学
生物化学
遗传学
作者
Yang Liu,Han–Soeb Yang,Yunxiang Chu,Yunhao Song,Lidan Ding,Bingtao Zhu,Wanli Zhai,Xuning Wang,Yanshen Kuang,Fei Ren,Baoqing Jia,Wei Wu,Xiongjun Ye,Yinyin Wang,Zhijie Chen
标识
DOI:10.1038/s41467-020-20636-9
摘要
Abstract Intestinal stem cells (ISCs) residing in the crypts are critical for the continual self-renewal and rapid recovery of the intestinal epithelium. The regulatory mechanism of ISCs is not fully understood. Here we report that CREPT, a recently identified tumor-promoting protein, is required for the maintenance of murine ISCs. CREPT is preferably expressed in the crypts but not in the villi. Deletion of CREPT in the intestinal epithelium of mice (Vil-CREPT KO ) results in lower body weight and slow migration of epithelial cells in the intestine. Vil-CREPT KO intestine fails to regenerate after X-ray irradiation and dextran sulfate sodium (DSS) treatment. Accordingly, the deletion of CREPT decreases the expression of genes related to the proliferation and differentiation of ISCs and reduces Lgr5 + cell numbers at homeostasis. We identify that CREPT deficiency downregulates Wnt signaling by impairing β-catenin accumulation in the nucleus of the crypt cells during regeneration. Our study provides a previously undefined regulator of ISCs.
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