Rees William D, Tandun Rene, Yau Enoch, Zachos Nicholas C, Steiner Theodore S
Department of Medicine, University of British Columbia, Vancouver, BC, Canada.
BC Children's Hospital Research Institute, Vancouver, BC, Canada.
Front Cell Dev Biol. 2020 Nov 12;8:583919. doi: 10.3389/fcell.2020.583919. eCollection 2020.
The intestinal epithelium is replenished every 3-4 days through an orderly process that maintains important secretory and absorptive functions while preserving a continuous mucosal barrier. Intestinal epithelial cells (IECs) derive from a stable population of intestinal stem cells (ISCs) that reside in the basal crypts. When intestinal injury reaches the crypts and damages IECs, a mechanism to replace them is needed. Recent research has highlighted the existence of distinct populations of acute and chronic damage-associated ISCs and their roles in maintaining homeostasis in several intestinal perturbation models. What remains unknown is how the damage-associated regenerative ISC population functions in the setting of chronic inflammation, as opposed to acute injury. What long-term consequences result from persistent inflammation and other cellular insults to the ISC niche? What particular "regenerative" cell types provide the most efficacious restorative properties? Which differentiated IECs maintain the ability to de-differentiate and restore the ISC niche? This review will cover the latest research on damage-associated regenerative ISCs and epigenetic factors that determine ISC fate, as well as provide opinions on future studies that need to be undertaken to understand the repercussions of the emergence of these cells, their contribution to relapses in inflammatory bowel disease, and their potential use in therapeutics for chronic intestinal diseases.
肠上皮每3 - 4天通过一个有序的过程进行更新，该过程在维持重要的分泌和吸收功能的同时保持连续的黏膜屏障。肠上皮细胞（IECs）来源于位于隐窝底部的稳定的肠干细胞（ISCs）群体。当肠道损伤累及隐窝并损害IECs时，就需要一种机制来替换它们。最近的研究强调了急性和慢性损伤相关的ISCs不同群体的存在及其在几种肠道扰动模型中维持内环境稳定的作用。尚不清楚的是，与急性损伤相反，损伤相关的再生性ISC群体在慢性炎症环境中如何发挥作用。持续的炎症和其他细胞损伤对ISC生态位会产生哪些长期后果？哪些特定的“再生”细胞类型具有最有效的修复特性？哪些分化的IECs保持去分化并恢复ISC生态位的能力？本综述将涵盖关于损伤相关的再生性ISCs和决定ISC命运的表观遗传因素的最新研究，并就未来需要开展的研究提供见解，以了解这些细胞出现的影响、它们对炎症性肠病复发的贡献以及它们在慢性肠道疾病治疗中的潜在用途。
