Tissue regeneration requires dynamic cellular adaptation to the wound environment. It is currently unclear how this is orchestrated at the cellular level and how cell fate is affected by severe tissue damage. Here we dissect cell fate transitions during colonic regeneration in a mouse dextran sulfate sodium (DSS) colitis model, and we demonstrate that the epithelium is transiently reprogrammed into a primitive state. This is characterized by de novo expression of fetal markers as well as suppression of markers for adult stem and differentiated cells. The fate change is orchestrated by remodeling the extracellular matrix (ECM), increased FAK/Src signaling, and ultimately YAP/TAZ activation. In a defined cell culture system recapitulating the extracellular matrix remodeling observed in vivo, we show that a collagen 3D matrix supplemented with Wnt ligands is sufficient to sustain endogenous YAP/TAZ and induce conversion of cell fate. This provides a simple model for tissue regeneration, implicating cellular reprogramming as an essential element.

中文翻译：

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YAP / TAZ依赖的结肠上皮重编程将ECM重塑与组织再生联系起来。

组织再生需要动态的细胞适应伤口环境。目前尚不清楚如何在细胞水平上对其进行协调以及严重的组织损伤如何影响细胞命运。在这里，我们剖析了小鼠葡聚糖硫酸钠（DSS）结肠炎模型中结肠再生过程中的细胞命运转变，并且我们证明了上皮被短暂地重新编程为原始状态。其特征在于胎儿标志物从头表达，以及抑制成年干细胞和分化细胞的标志物。通过重塑细胞外基质（ECM），增加FAK / Src信号传导并最终激活YAP / TAZ，可以安排命运的变化。在定义的细胞培养系统中，概括了体内观察到的细胞外基质重塑，我们显示，补充有Wnt配体的3D胶原蛋白基质足以维持内源性YAP / TAZ并诱导细胞命运的转化。这提供了用于组织再生的简单模型，暗示细胞重编程是必不可少的元素。