YAP/TAZ-Dependent Reprogramming of Colonic Epithelium Links ECM Remodeling to Tissue Regeneration.

IF 19.8 1区 医学 Q1 CELL & TISSUE ENGINEERING
Cell stem cell Pub Date : 2018-01-04 Epub Date: 2017-12-14 DOI:10.1016/j.stem.2017.11.001
Shiro Yui, Luca Azzolin, Martti Maimets, Marianne Terndrup Pedersen, Robert P Fordham, Stine L Hansen, Hjalte L Larsen, Jordi Guiu, Mariana R P Alves, Carsten F Rundsten, Jens V Johansen, Yuan Li, Chris D Madsen, Tetsuya Nakamura, Mamoru Watanabe, Ole H Nielsen, Pawel J Schweiger, Stefano Piccolo, Kim B Jensen
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引用次数: 382

Abstract

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.

Abstract Image

Abstract Image

Abstract Image

YAP/ taz依赖性结肠上皮重编程将ECM重塑与组织再生联系起来。
组织再生需要细胞动态适应伤口环境。目前尚不清楚这是如何在细胞水平上进行的,以及严重的组织损伤如何影响细胞命运。在这里,我们在小鼠葡聚糖硫酸钠(DSS)结肠炎模型中解剖结肠再生过程中的细胞命运转变,并证明上皮被短暂地重新编程为原始状态。其特点是胎儿标记物的新生表达以及成体干细胞和分化细胞标记物的抑制。这种命运的改变是通过重塑细胞外基质(ECM)、增加FAK/Src信号以及最终激活YAP/TAZ来协调的。在一个明确的细胞培养系统中,概括了在体内观察到的细胞外基质重塑,我们发现补充了Wnt配体的胶原3D基质足以维持内源性YAP/TAZ并诱导细胞命运的转化。这为组织再生提供了一个简单的模型,暗示细胞重编程是一个基本要素。
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来源期刊
Cell stem cell
Cell stem cell 生物-细胞生物学
CiteScore
37.10
自引率
2.50%
发文量
151
审稿时长
42 days
期刊介绍: Cell Stem Cell is a comprehensive journal covering the entire spectrum of stem cell biology. It encompasses various topics, including embryonic stem cells, pluripotency, germline stem cells, tissue-specific stem cells, differentiation, epigenetics, genomics, cancer stem cells, stem cell niches, disease models, nuclear transfer technology, bioengineering, drug discovery, in vivo imaging, therapeutic applications, regenerative medicine, clinical insights, research policies, ethical considerations, and technical innovations. The journal welcomes studies from any model system providing insights into stem cell biology, with a focus on human stem cells. It publishes research reports of significant importance, along with review and analysis articles covering diverse aspects of stem cell research.
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