Abstract：
Skeletal muscle repair and maintenance are directly and indirectly supported by interstitial cell populations such as vascular cells and fibro-adipogenic progenitors (FAPs), a subset of which express Twist2 and possess direct myogenic potential. Furthermore, work in rodents has highlighted the potential of pericytes to act as progenitor cells, giving rise to muscle cells and transdifferentiating into endothelial cells. However, less is understood about these populations in human skeletal muscle. Here, we performed single-cell RNA sequencing (scRNAseq) on ∼2,000 cells isolated from the human semitendinosus muscle of young individuals. This demonstrated the presence of a vascular-related cell type that expressed pericyte and pan-endothelial genes that we localized to large blood vessels within skeletal muscle cross sections and termed endothelial-like pericytes (ELPCs). RNA velocity analysis indicated that ELPCs may represent a \"transition state\" between endothelial cells and pericytes. Analysis of published scRNAseq data sets revealed evidence for ELPCs in trunk and heart musculature, which showed transcriptional similarity. In addition, we identified a subset of FAPs expressing TWIST2 mRNA and protein. Human TWIST2-expressing cells were anatomically and transcriptionally comparable to mouse Twist2 cells as they were restricted to the myofiber interstitium, expressed fibrogenic genes but lacked satellite cell markers, and colocalized with the FAPs marker PDGFRα in human muscle cross sections. Taken together, these results highlight the complexity of stromal cells residing in human skeletal muscle and support the utility of scRNAseq for discovery and characterization of poorly described cell populations.
摘要：
骨骼肌修复和维持是直接和间接支持的间质细胞群体，如血管细胞和纤维脂肪原祖细胞（FAP），其子集表达Twist2并具有直接生肌潜能。此外，在啮齿动物中的工作突出了周细胞作为祖细胞的潜力，产生肌肉细胞并转分化为内皮细胞。然而,对这些人群在人类骨骼肌中的了解较少。这里,我们对从年轻个体的人半腱肌分离的~2,000个细胞进行了单细胞RNA测序（scRNAseq）。这表明存在表达周细胞和泛内皮基因的血管相关细胞类型，我们将其定位在骨骼肌横截面内的大血管中，并称为内皮样周细胞（ELPC）。RNA速度分析表明，ELPCs可能代表内皮细胞和周细胞之间的“过渡状态”。对已发表的scRNAseq数据集的分析揭示了躯干和心脏肌肉组织中ELPC的证据，这显示了转录相似性。此外,我们鉴定了表达TWIST2mRNA和蛋白的FAP亚群。人类TWIST2表达细胞在解剖学和转录上与小鼠Twist2细胞相当，因为它们仅限于肌纤维间质，表达纤维化基因，但缺乏卫星细胞标记，并与人肌肉横截面中的FAP标记PDGFRα共定位。一起来看,这些结果突出了人骨骼肌中基质细胞的复杂性,并支持scRNAseq用于发现和表征描述不佳的细胞群的实用性.
