Department of Applied Human Sciences, University of Prince Edward Island, Charlottetown, Prince Edward Island, Canada.
Queen Elizabeth Hospital, Charlottetown, Prince Edward Island, Canada.
Am J Physiol Cell Physiol. 2022 Dec 1;323(6):C1586-C1600. doi: 10.1152/ajpcell.00364.2022. Epub 2022 Nov 7.
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 mRNA and protein. Human -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.
骨骼肌的修复和维持直接或间接地依赖于间质细胞群体，如血管细胞和成纤维脂肪祖细胞（FAPs），其中一部分表达 Twist2 并具有直接成肌潜能。此外，啮齿动物的研究工作强调了周细胞作为祖细胞的潜力，使其能够分化为肌肉细胞并转分化为内皮细胞。然而，人们对人类骨骼肌中的这些细胞群体了解较少。在这里，我们对来自年轻人的人半腱肌中约 2000 个细胞进行了单细胞 RNA 测序（scRNAseq）。这表明存在一种与血管相关的细胞类型，表达周细胞和泛内皮基因，我们将其定位于骨骼肌横切面上的大血管中，并将其命名为内皮样周细胞（ELPCs）。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 数据集的分析表明，在躯干和心脏肌肉中存在 ELPCs 的证据，它们具有转录相似性。此外，我们鉴定了表达 mRNA 和蛋白的 FAPs 亚群。表达的细胞在解剖学和转录上与小鼠 Twist2 细胞相似，因为它们局限于肌纤维间质，表达成纤维基因，但缺乏卫星细胞标志物，并且与人肌肉横切面上的 FAPs 标志物 PDGFRα 共定位。总之，这些结果强调了驻留在人类骨骼肌中的基质细胞的复杂性，并支持 scRNAseq 用于发现和描述描述不足的细胞群体的效用。
