Fibroblasts, custodians of tissue architecture and function, are no longer considered a monolithic entity across tissues and disease indications. Recent advances in single-cell technologies provide an unrestricted, high-resolution view of fibroblast heterogeneity that exists within and across tissues. In this review, we summarize a compendium of single-cell transcriptomic studies and provide a comprehensive accounting of fibroblast subsets, many of which have been described to occupy specific niches in tissues at homeostatic and pathologic states. Understanding this heterogeneity is particularly important in the context of cancer, as the diverse cancer-associated fibroblast (CAF) phenotypes in the tumor microenvironment (TME) are directly impacted by the expression phenotypes of their predecessors. Relationships between these heterogeneous populations often accompany and influence response to therapy in cancer and fibrosis. We further highlight the importance of integrating single-cell studies to deduce common fibroblast phenotypes across disease states, which will facilitate the identification of common signaling pathways, gene regulatory programs, and cell surface markers that are going to advance drug discovery and targeting.

中文翻译：

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成纤维细胞异质性的鸟瞰图：泛疾病、泛癌视角

成纤维细胞是组织结构和功能的监护人，不再被视为跨组织和疾病适应症的整体实体。单细胞技术的最新进展为存在于组织内和组织间的成纤维细胞异质性提供了不受限制的高分辨率视图。在这篇综述中，我们总结了单细胞转录组学研究纲要，并提供了对成纤维细胞亚群的全面说明，其中许多被描述为在稳态和病理状态下占据组织中的特定位置。了解这种异质性在癌症的背景下尤为重要，因为肿瘤微环境 (TME) 中多种癌症相关成纤维细胞 (CAF) 表型直接受到其前辈表达表型的影响。这些异质人群之间的关系通常伴随并影响对癌症和纤维化治疗的反应。我们进一步强调了整合单细胞研究以推断不同疾病状态的常见成纤维细胞表型的重要性，这将有助于识别将促进药物发现和靶向的常见信号通路、基因调控程序和细胞表面标记。