Karolinska Institutet/AstraZeneca Integrated Cardio Metabolic Centre, Blickagången 6, SE-14157, Huddinge, Sweden.
Department of Medicine Huddinge, Karolinska Institutet, SE-14157, Huddinge, Sweden.
Nat Commun. 2020 Aug 7;11(1):3953. doi: 10.1038/s41467-020-17740-1.
Many important cell types in adult vertebrates have a mesenchymal origin, including fibroblasts and vascular mural cells. Although their biological importance is undisputed, the level of mesenchymal cell heterogeneity within and between organs, while appreciated, has not been analyzed in detail. Here, we compare single-cell transcriptional profiles of fibroblasts and vascular mural cells across four murine muscular organs: heart, skeletal muscle, intestine and bladder. We reveal gene expression signatures that demarcate fibroblasts from mural cells and provide molecular signatures for cell subtype identification. We observe striking inter- and intra-organ heterogeneity amongst the fibroblasts, primarily reflecting differences in the expression of extracellular matrix components. Fibroblast subtypes localize to discrete anatomical positions offering novel predictions about physiological function(s) and regulatory signaling circuits. Our data shed new light on the diversity of poorly defined classes of cells and provide a foundation for improved understanding of their roles in physiological and pathological processes.
许多成年脊椎动物的重要细胞类型具有间充质起源，包括成纤维细胞和血管壁细胞。尽管它们的生物学重要性是毋庸置疑的，但器官内和器官间间充质细胞异质性的程度虽然已经得到认可，但尚未进行详细分析。在这里，我们比较了来自四个鼠肌肉器官（心脏、骨骼肌、肠道和膀胱）的成纤维细胞和血管壁细胞的单细胞转录谱。我们揭示了将成纤维细胞与壁细胞区分开来的基因表达特征，并提供了用于细胞亚型鉴定的分子特征。我们观察到成纤维细胞之间以及器官内存在显著的异质性，主要反映了细胞外基质成分表达的差异。成纤维细胞亚型定位于离散的解剖位置，为生理功能和调节信号回路提供了新的预测。我们的数据为定义不明确的细胞类群的多样性提供了新的认识，并为更好地理解它们在生理和病理过程中的作用奠定了基础。
