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Sox11在成肌祖细胞中富集,但对骨骼肌的发育和再生并非必需。

Sox11 is enriched in myogenic progenitors but dispensable for development and regeneration of skeletal muscle.

作者信息

Oprescu Stephanie N, Baumann Nick, Chen Xiyue, Sun Qiang, Zhao Yu, Yue Feng, Wang Huating, Kuang Shihuan

出版信息

bioRxiv. 2023 Mar 31:2023.03.30.534956. doi: 10.1101/2023.03.30.534956.

Abstract

Transcription factors (TFs) play key roles in regulating the differentiation and function of stem cells, including muscle satellite cells (MuSCs), a resident stem cell population responsible for postnatal regeneration of the skeletal muscle. Sox11 belongs to the Sry-related HMG-box (SOX) family of TFs that play diverse roles in stem cell behavior and tissue specification. Analysis of single-cell RNA-sequencing (scRNA-seq) datasets identify a specific enrichment of mRNA in differentiating but not quiescent MuSCs. Consistent with the scRNA-seq data, levels increase during differentiation of murine primary myoblasts in vitro. scRNA-seq data comparing muscle regeneration in young and old mice further demonstrate that expression is reduced in aged MuSCs. Age-related decline of expression is associated with reduced chromatin contacts within the topologically associated domains. Unexpectedly, Myod1 -driven deletion of in embryonic myoblasts has no effects on muscle development and growth, resulting in apparently healthy muscles that regenerate normally. Pax7 or Rosa26 driven (MuSC-specific or global) deletion of in adult mice similarly has no effects on MuSC differentiation or muscle regeneration. These results identify Sox11 as a novel myogenic differentiation marker with reduced expression in quiescent and aged MuSCs, but the specific function of Sox11 in myogenesis remain to be elucidated.

摘要

转录因子(TFs)在调节干细胞的分化和功能中发挥关键作用,这些干细胞包括肌肉卫星细胞(MuSCs),它是一种驻留干细胞群体,负责出生后骨骼肌的再生。Sox11属于Sry相关的HMG盒(SOX)转录因子家族,在干细胞行为和组织特化中发挥多种作用。对单细胞RNA测序(scRNA-seq)数据集的分析表明,在分化的而非静止的MuSCs中有特定的mRNA富集。与scRNA-seq数据一致,在体外小鼠原代成肌细胞分化过程中,其水平升高。比较年轻和老年小鼠肌肉再生的scRNA-seq数据进一步表明,在衰老的MuSCs中表达降低。与年龄相关的表达下降与拓扑相关结构域内染色质接触减少有关。出乎意料的是,在胚胎成肌细胞中Myod1驱动的缺失对肌肉发育和生长没有影响,产生的肌肉明显健康且能正常再生。在成年小鼠中,Pax7或Rosa26驱动的(MuSC特异性或全身性)缺失同样对MuSC分化或肌肉再生没有影响。这些结果确定Sox11是一种在静止和衰老的MuSCs中表达降低的新型肌源性分化标志物,但Sox11在肌生成中的具体功能仍有待阐明。

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