PDGFRα+ mesenchymal progenitor cells are associated with pathological fibro-adipogenic processes. Conversely, a beneficial role for these cells during homeostasis or in response to revascularization and regeneration stimuli is suggested, but remains to be defined. We studied the molecular profile and function of PDGFRα+ cells in order to understand the mechanisms underlying their role in fibrosis versus regeneration. We show that PDGFRα+ cells are essential for tissue revascularization and restructuring through injury-stimulated remodeling of stromal and vascular components, context-dependent clonal expansion, and ultimate removal of pro-fibrotic PDGFRα+-derived cells. Tissue ischemia modulates the PDGFRα+ phenotype toward cells capable of remodeling the extracellular matrix and inducing cell-cell and cell-matrix adhesion, likely favoring tissue repair. Conversely, pathological healing occurs if PDGFRα+-derived cells persist as terminally differentiated mesenchymal cells. These studies support a context-dependent "yin-yang" biology of tissue-resident mesenchymal progenitor cells, which possess an innate ability to limit injury expansion while also promoting fibrosis in an unfavorable environment.

中文翻译：

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驻留在组织中的PDGFRα+祖细胞在上下文和时空依赖的方式下促进纤维化与愈合。

PDGFRα+间充质祖细胞与病理性纤维成脂过程有关。相反，提出了这些细胞在稳态过程中或对血运重建和再生刺激的响应中的有益作用，但尚待确定。我们研究了PDGFRα+细胞的分子概况和功能，以了解其在纤维化与再生中的作用基础机制。我们显示，PDGFRα+细胞对于组织血运重建和重组是必不可少的，它通过基质和血管成分的损伤刺激重塑，背景相关的克隆扩增以及促纤维化PDGFRα+衍生细胞的最终清除而获得。组织缺血会向能够重塑细胞外基质并诱导细胞与细胞和细胞基质粘附的细胞调节PDGFRα+表型，可能有利于组织修复。相反，如果PDGFRα+衍生的细胞作为终末分化的间充质细胞持续存在，则会发生病理学愈合。这些研究支持组织驻留的间充质祖细胞的上下文相关的“阴阳”生物学，其固有的能力是限制损伤的扩展，同时在不利的环境中促进纤维化。