High-Dimensional Single-Cell Cartography Reveals Novel Skeletal Muscle-Resident Cell Populations
High-Dimensional Single-Cell Cartography Reveals Novel Skeletal Muscle-Resident Cell Populations
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DOI：
10.1016/j.molcel.2019.02.026
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发表时间：
2019-05-02
期刊：
影响因子：
16
通讯作者：
Le Grand, Fabien
中科院分区：
文献类型：
--
作者：
Giordani, Lorenzo;He, Gary J.;Le Grand, Fabien
成体组织修复和再生需要能够自我更新并产生分化后代的干祖细胞。骨骼肌再生能力依赖于肌肉卫星细胞（MuSC）及其与生态位内不同细胞类型的相互作用。然而，我们对骨骼肌组织细胞组成的了解是有限的。在这里，使用单细胞RNA测序和质谱细胞术的组合方法，我们精确地绘制了成年小鼠肌肉中10种不同的单核细胞类型。我们还表征了基因特征并确定了每种细胞类型的关键鉴别标记。我们在间质区室中鉴定了两个之前研究不足的细胞群。一种是在体外表达转录因子scleraxis并产生腱细胞。第二种表达平滑肌和间充质细胞（SMMCs）的标志物，虽然与MuSC不同，但表现出肌原性潜力，并促进移植后的MuSC植入。这里提出的蓝图产生了对肌肉驻留细胞类型身份的重要见解，并可用于研究肌肉疾病。
Adult tissue repair and regeneration require stem-progenitor cells that can self-renew and generate differentiated progeny. Skeletal muscle regenerative capacity relies on muscle satellite cells (MuSCs) and their interplay with different cell types within the niche. However, our understanding of skeletal muscle tissue cellular composition is limited. Here, using a combined approach of single-cell RNA sequencing and mass cytometry, we precisely mapped 10 different mononuclear cell types in adult mouse muscle. We also characterized gene signatures and determined key discriminating markers of each cell type. We identified two previously understudied cell populations in the interstitial compartment. One expresses the transcription factor scleraxis and generated tenocytes in vitro. The second expresses markers of smooth muscle and mesenchymal cells (SMMCs) and, while distinct from MuSCs, exhibited myogenic potential and promoted MuSC engraftment following transplantation. The blueprint presented here yields crucial insights into muscle-resident cell-type identities and can be exploited to study muscle diseases.