肠上皮干细胞研究进展

Intestinal stem cells: current understanding of functions and regulation

肠上皮是人体更新最快的组织,位于其底部隐窝结构中的干细胞是它快速更新的驱动力所在.Lgr5+细胞是最主要的肠上皮干细胞类群,它可以分化产生所有的肠上皮细胞类群.Lgr5+肠干细胞的命运受Wnt,BMP,Notch,EGF和Hippo等生长发育信号通路的调控,以及肠道微生物和人体代谢水平的影响.肠上皮干细胞的稳态维持与肠道疾病发生紧密相关,其功能缺失会引起消化吸收功能下降、炎症发生,而其过度激活导致的增生又会诱发肿瘤,形成结直肠癌.对肠上皮干细胞的研究既可以加深对于肠上皮快速更新机制的了解,又可以为治疗结直肠癌等肠道疾病提供新的启示.

Lgr5^＋ intestinal stem cells（ISCs） residing at the intestinal crypt bottom give rise to all types of cells in intestinal epithelium and drive its fast renewal. Their fates are determined by environmental cues, including Wnt, BMP, Notch, EGF and Hippo signaling, as well as microbiota and metabolism. ISCs play a crucial role in intestinal disease development. Their degeneration leads to colitis, while their over-growth drives tumor formation. Therefore, the investigation of the mechanisms underlying ISCs self-renewal and differentiation is critical to understand the homeostatic maintenance of intestinal epithelium and facilitate the treatment of intestinal diseases.