Although heterogeneity is recognized within the murine satellite cell pool, a comprehensive understanding of distinct subpopulations and their functional relevance in human satellite cells is lacking. We used a combination of single cell RNA sequencing and flow cytometry to identify, distinguish, and physically separate novel subpopulations of human PAX7+ satellite cells (Hu-MuSCs) from normal muscles. We found that, although relatively homogeneous compared to activated satellite cells and committed progenitors, the Hu-MuSC pool contains clusters of transcriptionally distinct cells with consistency across human individuals. New surface marker combinations were enriched in transcriptional subclusters, including a subpopulation of Hu-MuSCs marked by CXCR4/CD29/CD56/CAV1 (CAV1+). In vitro, CAV1+ Hu-MuSCs are morphologically distinct, and characterized by resistance to activation compared to CAV1- Hu-MuSCs. In vivo, CAV1+ Hu-MuSCs demonstrated increased engraftment after transplantation. Our findings provide a comprehensive transcriptional view of normal Hu-MuSCs and describe new heterogeneity, enabling separation of functionally distinct human satellite cell subpopulations.

中文翻译：

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通过单细胞RNA测序鉴定功能异源的人类卫星细胞

尽管在鼠类卫星细胞库中认识到异质性，但仍缺乏对不同亚群及其在人类卫星细胞中的功能相关性的全面了解。我们使用单细胞RNA测序和流式细胞仪的组合来识别，区分和物理分离正常肌肉中人PAX7 +卫星细胞（Hu-MuSCs）的新型亚群。我们发现，尽管与活化的卫星细胞和定型祖细胞相比，Hu-MuSC库相对而言是同质的，但它包含转录上不同的细胞簇，在人类个体之间具有一致性。新的表面标记组合丰富了转录亚簇，包括以CXCR4 / CD29 / CD56 / CAV1（CAV1 +）标记的Hu-MuSC的亚群。体外，CAV1 + Hu-MuSCs在形态上截然不同，并且与CAV1- Hu-MuSCs相比，具有对激活的抵抗力。在体内，CAV1 + Hu-MuSCs在移植后表现出更高的植入率。我们的发现为正常的Hu-MuSCs提供了全面的转录观点，并描述了新的异质性，从而能够分离功能上不同的人类卫星细胞亚群。