Functionally heterogeneous human satellite cells identified by single cell RNA sequencing
Functionally heterogeneous human satellite cells identified by single cell RNA sequencing
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DOI：
10.7554/elife.51576
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发表时间：
2020-04-01
期刊：
影响因子：
7.7
通讯作者：
Pomerantz, Jason H.
中科院分区：
文献类型：
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作者：
Barruet, Emilie;Garcia, Steven M.;Pomerantz, Jason H.
尽管在小鼠卫星细胞池中认识到异质性，但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测序和流式细胞术相结合的方法，从正常肌肉中鉴定、区分和物理分离人类PAX7+卫星细胞（Hu-MuSCs）的新亚群。我们发现，尽管与激活的卫星细胞和承诺的祖细胞相比，Hu-MuSC池相对均匀，但它包含转录不同的细胞簇，在人类个体中具有一致性。新的表面标记组合在转录亚簇中富集，包括由CXCR4/CD29/CD56/CAV1 （CAV1+）标记的Hu-MuSCs亚群。在体外，与CAV1- hu - musc相比，CAV1+ hu - musc在形态上是不同的，并且具有抗活化的特征。在体内，CAV1 + hu - musc在移植后表现出更多的植入。我们的研究结果提供了正常hu - musc的全面转录视图，并描述了新的异质性，使功能不同的人类卫星细胞亚群分离成为可能。
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.