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Abstract：
Organ fibrosis causes collagen fiber overgrowth and impairs organ function. Cardiac fibrosis after myocardial infarction impairs cardiac function significantly, pulmonary fibrosis reduces gas exchange efficiency, and liver fibrosis disturbs the natural function of the liver. Its development is associated with the differentiation of fibroblasts into myofibroblasts and increased collagen synthesis. Fibrosis has organ specificity, defined by the heterogeneity of fibroblasts. Although this heterogeneity is established during embryonic development, it has not been defined yet. Fibroblastic differentiation of induced pluripotent stem cells (iPSCs) recapitulates the process by which fibroblasts acquire diversity. Here, we differentiated iPSCs into cardiac, hepatic, and dermal fibroblasts and analyzed their properties using single-cell RNA sequencing. We observed characteristic subpopulations with different ratios in each organ-type fibroblast group, which contained both resting and distinct ACTA2+ myofibroblasts. These findings provide crucial information on the ontogeny-based heterogeneity of fibroblasts, leading to the development of therapeutic strategies to control fibrosis.
摘要：
器官纤维化导致胶原纤维过度生长并损害器官功能。心肌梗死后心脏纤维化显著损害心功能，肺纤维化降低了气体交换效率，肝纤维化会扰乱肝脏的自然功能。它的发育与成纤维细胞分化为肌成纤维细胞和胶原蛋白合成增加有关。纤维化具有器官特异性，由成纤维细胞的异质性定义。尽管这种异质性是在胚胎发育过程中建立的，尚未定义。诱导多能干细胞（iPSC）的成纤维细胞分化概括了成纤维细胞获得多样性的过程。这里,我们将iPSCs分化为心脏，肝，和真皮成纤维细胞，并使用单细胞RNA测序分析了它们的特性。我们观察到每个器官类型成纤维细胞组中具有不同比例的特征性亚群，其中包含静息和独特的ACTA2肌成纤维细胞。这些发现提供了关于成纤维细胞基于个体发育的异质性的关键信息，导致控制纤维化的治疗策略的发展。
