研究揭示結腸幹細胞損傷修復周期
作者：
小柯機器人發布時間：2019/11/8 12:55:54
美國聖路易斯華盛頓大學醫學院Thaddeus S. Stappenbeck課題組取得一項新進展。他們利用長期體外培養系統捕捉到結腸幹細胞的損傷修復周期。這一研究成果2019年11月7日在線發表於國際學術期刊《細胞》。
研究人員確定了與Hopx蛋白陽性結腸炎相關的再生幹細胞（CARSC）群體，其功能有助於結腸炎的小鼠模型中的黏膜修復。富含胎兒樣標記物的Hopx陽性CARSC能夠短暫產生肥大的隱窩，後者有助於再生。重要的是，研究人員建立了一個長期的、自組織的二維（2D）上皮單層系統，以對Hopx 陽性CARSC的再生特性和響應進行建模。該系統可以重現體內發生的上皮改變的「動態平衡損傷再生」周期。使用該系統，研究人員發現炎症性腸病中常見的低氧和內質網應激在此過程中介導了細胞狀態的周期性轉換。
據介紹，結腸上皮細胞經常經受過度的炎症反應，會經歷多輪損傷和修復。目前尚不清楚介導此過程的反應性幹細胞，部分原因是缺乏體外模型，即需要能夠概括損傷和修復過程中體內發生的關鍵上皮變化。
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
Cell：《細胞》，創刊於1974年。隸屬於細胞出版社，最新IF：36.216