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Long-Term Culture Captures Injury-Repair Cycles of Colonic Stem Cells.
Cell ( IF 45.5 ) Pub Date : 2019-11-07 , DOI: 10.1016/j.cell.2019.10.015 Yi Wang 1 , I-Ling Chiang 1 , Takahiro E Ohara 1 , Satoru Fujii 1 , Jiye Cheng 2 , Brian D Muegge 1 , Aaron Ver Heul 1 , Nathan D Han 2 , Qiuhe Lu 1 , Shanshan Xiong 1 , Feidi Chen 1 , Chin-Wen Lai 1 , Hana Janova 1 , Renee Wu 1 , Charles E Whitehurst 3 , Kelli L VanDussen 1 , Ta-Chiang Liu 1 , Jeffrey I Gordon 2 , L David Sibley 4 , Thaddeus S Stappenbeck 1
Cell ( IF 45.5 ) Pub Date : 2019-11-07 , DOI: 10.1016/j.cell.2019.10.015 Yi Wang 1 , I-Ling Chiang 1 , Takahiro E Ohara 1 , Satoru Fujii 1 , Jiye Cheng 2 , Brian D Muegge 1 , Aaron Ver Heul 1 , Nathan D Han 2 , Qiuhe Lu 1 , Shanshan Xiong 1 , Feidi Chen 1 , Chin-Wen Lai 1 , Hana Janova 1 , Renee Wu 1 , Charles E Whitehurst 3 , Kelli L VanDussen 1 , Ta-Chiang Liu 1 , Jeffrey I Gordon 2 , L David Sibley 4 , Thaddeus S Stappenbeck 1
Affiliation
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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.
中文翻译：
长期培养捕获结肠干细胞的损伤修复周期。
结肠上皮可以经历多轮损伤和修复，通常是对过度炎症的反应。介导这一过程的反应性干细胞尚不清楚，部分原因是缺乏概括体内损伤和修复过程中发生的关键上皮变化的体外模型。在这里，我们鉴定了 Hopx+ 结肠炎相关再生干细胞 (CARSC) 群体，其功能有助于结肠炎小鼠模型中的粘膜修复。 Hopx+ CARSC 富含胎儿样标记，短暂地从已知促进再生的肥大隐窝中产生。重要的是，我们建立了一个长期的、自组织的二维（2D）上皮单层系统来模拟 Hopx+ CARSC 的再生特性和反应。该系统可以重现体内发生的上皮改变的“稳态-损伤-再生”循环。使用该系统，我们发现缺氧和内质网应激（炎症性肠病中常见的损伤）介导了这一过程中细胞状态的循环转换。
更新日期：2019-11-09
中文翻译：
长期培养捕获结肠干细胞的损伤修复周期。
结肠上皮可以经历多轮损伤和修复，通常是对过度炎症的反应。介导这一过程的反应性干细胞尚不清楚，部分原因是缺乏概括体内损伤和修复过程中发生的关键上皮变化的体外模型。在这里，我们鉴定了 Hopx+ 结肠炎相关再生干细胞 (CARSC) 群体，其功能有助于结肠炎小鼠模型中的粘膜修复。 Hopx+ CARSC 富含胎儿样标记，短暂地从已知促进再生的肥大隐窝中产生。重要的是，我们建立了一个长期的、自组织的二维（2D）上皮单层系统来模拟 Hopx+ CARSC 的再生特性和反应。该系统可以重现体内发生的上皮改变的“稳态-损伤-再生”循环。使用该系统，我们发现缺氧和内质网应激（炎症性肠病中常见的损伤）介导了这一过程中细胞状态的循环转换。
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