Fibroblasts are non-hematopoietic structural cells that define the architecture of organs, support the homeostasis of tissue-resident cells and play key roles in fibrosis, cancer, autoimmunity and wound healing. Recent studies have described fibroblast heterogeneity within individual tissues. However, the field lacks a definition of fibroblasts at single-cell resolution across tissues in healthy and diseased organs. Here, we integrated single-cell RNA transcriptomic data from ~150,000 fibroblast cells derived from 16 steady- and 11 perturbed-state mouse organs into fibroblast atlases. These data revealed two universal fibroblast cell subtypes, marked by expression of Pi16 or Col15a1, in all tissues; it also revealed discrete subsets of five specialized fibroblast subtypes in steady-state tissues and three activated fibroblast subtypes in perturbed or diseased tissues. These subsets were transcriptionally shaped by microenvironmental context rather than tissue-type alone. Inference of fibroblast lineage structure from the murine steady-state and perturbed-state fibroblast atlases suggested that specialized and activated subtypes are developmentally related to universal tissue-resident fibroblasts. Analysis of human samples revealed that fibroblast subtypes found in mice are conserved between species, including universal fibroblasts and activated phenotypes associated with pathogenicity in human cancer, fibrosis, arthritis and inflammation. In sum, a cross-species and pan-tissue approach to transcriptomics at single-cell resolution enabled us to define the organizing principles of the fibroblast lineage in health and disease.

中文翻译：

---

跨组织单细胞转录组学揭示健康和疾病中成纤维细胞的组织原理

成纤维细胞是定义器官结构的非造血结构细胞，支持组织驻留细胞的稳态，并在纤维化，癌症，自身免疫和伤口愈合中起关键作用。最近的研究描述了单个组织内的成纤维细胞异质性。然而，该领域缺乏健康和患病器官中跨组织单细胞分辨率的成纤维细胞的定义。在这里，我们将来自16个稳定状态小鼠器官和11个扰动状态小鼠器官的150,000个成纤维细胞的单细胞RNA转录组数据整合到成纤维细胞地图集中。这些数据揭示了两种普遍的成纤维细胞亚型，在所有组织中均以Pi16或Col15a1的表达为标志。它也揭示了稳态组织中五种特殊成纤维细胞亚型的离散子集，以及在受扰或患病的组织中三种活化的成纤维细胞亚型的离散子集。这些子集是通过微环境环境而不是单独的组织类型转录成形的。从鼠的稳态和扰动状态成纤维细胞图谱推断成纤维细胞谱系结构表明，专门化和激活的亚型与通用组织驻留型成纤维细胞在发育上相关。对人体样品的分析表明，在小鼠中发现的成纤维细胞亚型在物种之间是保守的，包括通用成纤维细胞和与人类癌症，纤维化，关节炎和炎症中的致病性相关的活化表型。总共，