► Wang Y, Chiang IL, Ohara TE, et al. Longterm culture captures injuryrepair cycles of colonic stem cells. Cell 2019; 179:1144–59. A stem cell population that mediates regeneration in colitis is unidentified. This is in part due to the challenge of an in vitro epithelial system with the continuous process of damage and repair. The authors used a chemical induced model of colitis (dextran sulphate sodium (DSS)) to show that crypts became atrophic during injury, with reduced expression of Lgr5 and Hopx. Subsequently hypertrophic crypts appeared adjacent to ulcers, and Hopx expression reemerged in these crypts. An inducible Hopxlabelled mouse model showed that the Hopx positive cells also expressed the foetallike marker Tacstd2. The Hopx cells could be lineage traced and gave rise to multiple differentiated cell lines. Sorted Hopx+ cells could form spheroids in culture. Ablation of Hopx cells after DSS injury led to apoptosis of the hypertrophic crypts and shorter colons. An in vitro epithelial monolayer was created by dissociating colonic spheroids into single cells and plating onto Transwell membranes submerged in medium for 7 days, before exposing them to an air–liquid interface (ALI). Hopx, but not Lgr5, labelled cells were expressed at the start of regeneration, which gave rise to the monolayer. Resubmerging and then reexposing the monolayer to the ALI recapitulated the injuryregeneration cycle. Hopx was temporarily lost then reemerged. Cellular stress was mediated by low oxygen tension, as it induced HIF1mediated signalling. The authors give evidence that Hopx+ cells function as regenerative stem cells in colitis and oxygen tension acts as a switch between injury and regeneration.

中文翻译：

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文献中的 GI 亮点

► Wang Y、Chiang IL、Ohara TE 等。长期培养捕获结肠干细胞的损伤修复周期。细胞 2019；179:1144-59。介导结肠炎再生的干细胞群尚不清楚。这部分是由于体外上皮系统的挑战与持续的损伤和修复过程。作者使用化学诱导的结肠炎模型（硫酸葡聚糖钠 (DSS)）显示隐窝在损伤期间萎缩，Lgr5 和 Hopx 表达降低。随后在溃疡附近出现肥大的隐窝，并且在这些隐窝中重新出现 Hopx 表达。诱导型 Hopx 标记的小鼠模型显示 Hopx 阳性细胞也表达了类似胎儿的标记 Tacstd2。Hopx 细胞可以进行谱系追踪并产生多种分化的细胞系。分选的 Hopx+ 细胞可以在培养中形成球体。DSS 损伤后 Hopx 细胞的消融导致肥厚的隐窝和较短的结肠细胞凋亡。体外上皮单层是通过将结肠球体分离成单个细胞并铺在浸没在培养基中 7 天的 Transwell 膜上，然后将它们暴露于气液界面 (ALI) 来创建的。Hopx，但不是 Lgr5，标记的细胞在再生开始时表达，从而产生单层。重新淹没然后将单层重新暴露于 ALI 概括了损伤再生循环。Hopx 暂时丢失然后重新出现。细胞应激由低氧张力介导，因为它诱导 HIF1 介导的信号传导。