动物造模,小鼠肠干细胞 z-bio 2021-02-21 293

　　Colorectal cancer is one of the cancers with the highest incidence and mortality in China, and almost all intestinal cancer cells are derived from intestinal epithelial cells. The continuous renewal ability of the intestinal epithelium is mainly maintained by the intestinal stem cells in the crypt. The most studied intestinal stem cells are Lgr5-positive stem cells. The microenvironment in which stem cells are located and the signal factors that regulate stem cells play a very critical role in maintaining stem cell proliferation, differentiation and intestinal epithelial cell homeostasis. Therefore, studying the regulation of stem cell proliferation and differentiation plays a very important role in revealing the pathogenesis of colorectal cancer. The laboratory of Professor Chang Zhijie of Tsinghua University and Peking University People’s Hospital jointly published a titled "CREPT is required for murine epithelial regeneration by regulating the function of mouse intestinal stem cells" in the journal Nature Communications. stem cell maintenance during intestinal regeneration).

　　 CREPT is a tumor gene cloned in the laboratory of Professor Chang Zhijie. It can promote tumor growth and cell proliferation, and is highly expressed in a variety of cancer tissues. Many papers have been published showing that CREPT is a potential tumor targeted therapy marker gene. This work proved for the first time that intestinal epithelial cells lacking CREPT cannot regenerate after being injured, and confirmed the important regulatory role of CREPT gene on Lgr5 + intestinal stem cells, providing a theoretical basis for exploring the pathogenesis of colorectal cancer. The study constructed a mouse model of colorectal cancer and a variety of gene knockout mouse models, and by simulating a variety of injury conditions, it was found that after knocking out CREPT in intestinal epithelial cells, the weight of the mice was significantly reduced, and the intestinal epithelium was unable to recover from X- Ray irradiation or DSS treatment regenerates damage, and the number of Lgr5 + stem cells drops sharply. In the in vitro culture experiment, the crypt cells knocked out of CREPT could not form intestinal organoids.

　　 Further high-throughput sequencing analysis proved that CREPT can regulate the proliferation and differentiation of Lgr5 + stem cells through the Wnt-β-catenin signaling pathway, thereby promoting intestinal epithelial regeneration and repair.