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A reference single-cell transcriptomic atlas of human skeletal muscle tissue reveals bifurcated muscle stem cell populations.
Skeletal Muscle ( IF 4.9 ) Pub Date : 2020-07-06 , DOI: 10.1186/s13395-020-00236-3
Andrea J De Micheli 1, 2 , Jason A Spector 1, 3 , Olivier Elemento 2 , Benjamin D Cosgrove 1
Affiliation  

Single-cell RNA-sequencing (scRNA-seq) facilitates the unbiased reconstruction of multicellular tissue systems in health and disease. Here, we present a curated scRNA-seq dataset of human muscle samples from 10 adult donors with diverse anatomical locations. We integrated ~ 22,000 single-cell transcriptomes using Scanorama to account for technical and biological variation and resolved 16 distinct populations of muscle-resident cells using unsupervised clustering of the data compendium. These cell populations included muscle stem/progenitor cells (MuSCs), which bifurcated into discrete “quiescent” and “early-activated” MuSC subpopulations. Differential expression analysis identified transcriptional profiles altered in the activated MuSCs including genes associated with aging, obesity, diabetes, and impaired muscle regeneration, as well as long non-coding RNAs previously undescribed in human myogenic cells. Further, we modeled ligand-receptor cell-communication interactions and observed enrichment of the TWEAK-FN14 pathway in activated MuSCs, a characteristic signature of muscle wasting diseases. In contrast, the quiescent MuSCs have enhanced expression of the EGFR receptor, a recognized human MuSC marker. This work provides a new benchmark reference resource to examine human muscle tissue heterogeneity and identify potential targets in MuSC diversity and dysregulation in disease contexts.

中文翻译:

人体骨骼肌组织的参考单细胞转录组图谱显示了分叉的肌肉干细胞群。

单细胞RNA测序(scRNA-seq)有助于健康和疾病中多细胞组织系统的无偏重建。在这里,我们介绍了来自10个成年供体的,具有不同解剖位置的人类肌肉样品的精选scRNA-seq数据集。我们使用Scanorama整合了约22,000个单细胞转录组,以解决技术和生物学差异,并使用数据手册的无监督聚类解决了16个不同的肌肉驻留细胞群体。这些细胞群包括肌肉干/祖细胞(MuSCs),它们分为离散的“静态”和“早期激活” MuSC亚群。差异表达分析确定了激活的MuSC中转录的改变,包括与衰老,肥胖,糖尿病和肌肉再生受损相关的基因,以及人类成肌细胞中以前未描述的长非编码RNA。此外,我们对配体-受体细胞-通讯相互作用进行了建模,并观察到了活化的MuSCs中TWEAK-FN14途径的富集,这是肌肉萎缩性疾病的特征性标志。相反,静止的MuSC具有增强的EGFR受体(公认的人类MuSC标记)的表达。这项工作提供了一个新的基准参考资源,以检查人类肌肉组织的异质性,并确定疾病背景下MuSC多样性和失调的潜在靶标。静止的MuSC具有增强的EGFR受体(公认的人类MuSC标记)的表达。这项工作提供了一个新的基准参考资源,以检查人类肌肉组织的异质性,并确定疾病背景下MuSC多样性和失调的潜在靶标。静止的MuSC具有增强的EGFR受体(公认的人类MuSC标记)的表达。这项工作提供了一个新的基准参考资源,以检查人类肌肉组织的异质性,并确定疾病背景下MuSC多样性和失调的潜在靶标。
更新日期:2020-07-24
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