小柯机器人

美国圣路易斯华盛顿大学医学院Thaddeus S. Stappenbeck课题组取得一项新进展。他们利用长期体外培养系统捕捉到结肠干细胞的损伤修复周期。这一研究成果2019年11月7日在线发表于国际学术期刊《细胞》。

研究人员确定了与Hopx蛋白阳性结肠炎相关的再生干细胞（CARSC）群体，其功能有助于结肠炎的小鼠模型中的粘膜修复。富含胎儿样标记物的Hopx阳性CARSC能够短暂产生肥大的隐窝，后者有助于再生。重要的是，研究人员建立了一个长期的、自组织的二维（2D）上皮单层系统，以对Hopx 阳性CARSC的再生特性和响应进行建模。该系统可以重现体内发生的上皮改变的“动态平衡损伤再生”周期。使用该系统，研究人员发现炎症性肠病中常见的低氧和内质网应激在此过程中介导了细胞状态的周期性转换。

据介绍，结肠上皮细胞经常经受过度的炎症反应，会经历多轮损伤和修复。目前尚不清楚介导此过程的反应性干细胞，部分原因是缺乏体外模型，即需要能够概括损伤和修复过程中体内发生的关键上皮变化。

附：英文原文

Title: Long-Term Culture Captures Injury-Repair Cycles of Colonic Stem Cells

Author: Yi Wang, I-Ling Chiang, Takahiro E. Ohara, Satoru Fujii, Jiye Cheng, Brian D. Muegge, Aaron Ver Heul, Nathan D. Han, Qiuhe Lu, Shanshan Xiong, Feidi Chen, Chin-Wen Lai, Hana Janova, Renee Wu, Charles E. Whitehurst, Kelli L. VanDussen, Ta-Chiang Liu, Jeffrey I. Gordon, L. David Sibley, Thaddeus S. Stappenbeck

Issue&Volume: November 07, 2019

Abstract:The colonic epithelium can undergo multiple rounds of damage and repair, often in response to excessive inflammation. The responsive stem cell that mediates this process is unclear, in part because of a lack of in vitro models that recapitulate key epithelial changes that occur in vivo during damage and repair. Here, we identify a Hopx+ colitis-associated regenerative stem cell (CARSC) population that functionally contributes to mucosal repair in mouse models of colitis. Hopx+ CARSCs, enriched for fetal-like markers, transiently arose from hypertrophic crypts known to facilitate regeneration. Importantly, we established a long-term, self-organizing two-dimensional (2D) epithelial monolayer system to model the regenerative properties and responses of Hopx+ CARSCs. This system can reenact the “homeostasis-injury-regeneration” cycles of epithelial alterations that occur in vivo. Using this system, we found that hypoxia and endoplasmic reticulum stress, insults commonly present in inflammatory bowel diseases, mediated the cyclic switch of cellular status in this process.

DOI: 10.1016/j.cell.2019.10.015

Source: https://www.cell.com/cell/fulltext/S0092-8674(19)31165-1