肠干细胞及其调控的当代快照。

A contemporary snapshot of intestinal stem cells and their regulation.

机构信息

A⁎STAR Institute of Medical Biology, 138648 Singapore, Singapore.

A⁎STAR Institute of Medical Biology, 138648 Singapore, Singapore; Cancer Research Institute, Kanazawa University, Kakuma-machi, Kanazawa 920-1192, Japan; Centre for Regenerative Medicine, The University of Edinburgh, 47 Little France Crescent, Edinburgh EH16 4TJ, UK; School of Biological Sciences, Nanyang Technological University, Singapore 308232, Singapore.

出版信息

Differentiation. 2019 Jul-Aug;108:3-7. doi: 10.1016/j.diff.2019.01.004. Epub 2019 Jan 25.

DOI:10.1016/j.diff.2019.01.004

PMID:30711339

Abstract

Intestinal stem cells (ISCs) marked by Lgr5 are located at the bottom of the epithelial crypt compartment. Canonical Wnt signaling, activated by Wnt/Rspo ligands, determines the stem cell identity of Lgr5 + ISCs and is strictly regulated by the ISC niche. Emerging evidence indicates that both epithelial and stromal compartments provide the requisite Wnt/Rspo ligands, confining the ISC niche to the lower crypt regions of the intestine. Recent studies have also shown that the ISC niche can reprogram differentiated cells to replenish lost ISCs following tissue injury, accounting for the epithelial cell plasticity within the crypt compartment. Here we review these recent advances and discuss the role of canonical Wnt signaling in maintaining homeostasis and effecting cell plasticity following tissue injury in the intestine, which could reveal potential novel therapeutic opportunities in the clinic.

摘要

肠干细胞（ISCs）由 Lgr5 标记，位于上皮隐窝隔室的底部。经典的 Wnt 信号通路被 Wnt/Rspo 配体激活，决定了 Lgr5+ISCs 的干细胞特性，并且受到 ISC 龛的严格调控。新出现的证据表明，上皮和基质隔室都提供了必需的 Wnt/Rspo 配体，将 ISC 龛限制在肠道的下部隐窝区域。最近的研究还表明，ISC 龛可以重编程分化细胞，在组织损伤后补充丢失的 ISC，这解释了隐窝隔室内上皮细胞的可塑性。在这里，我们综述了这些最新进展，并讨论了经典 Wnt 信号通路在维持肠道组织内稳态和损伤后影响细胞可塑性中的作用，这可能为临床提供潜在的新的治疗机会。