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

Sox11 is enriched in myogenic progenitors but dispensable for development and regeneration of the skeletal muscle.
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DOI:
10.1186/s13395-023-00324-0
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发表时间:
2023-09-13
期刊:
影响因子:
4.9
通讯作者:
--
中科院分区:
医学2区
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--
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转录因子(TF)在调节干细胞(包括肌肉卫星细胞(MuSC))的分化和功能中起关键作用,所述肌肉卫星细胞是负责骨骼肌的出生后再生的常驻干细胞群体。Sox 11属于Sry相关的HMG盒(SOX)家族,在干细胞行为和组织特异性中发挥不同作用。对单细胞RNA测序(scRNA-seq)数据集的分析鉴定了Sox 11 mRNA在分化中而非静止MuSC中的特异性富集。与scRNA-seq数据一致,Sox 11水平在体外小鼠原代成肌细胞分化期间增加。比较年轻和老年小鼠肌肉再生的scRNA-seq数据进一步表明,Sox 11表达在老年MuSC中减少。Sox 11表达的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,Myod 1Cre驱动的胚胎成肌细胞中Sox 11的缺失对肌肉发育和生长没有影响,导致明显健康的肌肉正常再生。在成年小鼠中Pax 7 CreER或Rosa 26 CreER驱动的(MuSC特异性或全局)Sox 11缺失同样对MuSC分化或肌肉再生没有影响。这些结果将Sox 11鉴定为一种新的肌源性分化标志物,其在静止和老化的MuSC中表达减少,但Sox 11在肌发生中的具体功能仍有待阐明。在线版本包含补充材料,可通过10.1186/s13395-023-00324-0获得。
Transcription factors (TFs) play key roles in regulating 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 Sox11 mRNA in differentiating but not quiescent MuSCs. Consistent with the scRNA-seq data, Sox11 levels increase during differentiation of murine primary myoblasts in vitro. scRNA-seq data comparing muscle regeneration in young and old mice further demonstrate that Sox11 expression is reduced in aged MuSCs. Age-related decline of Sox11 expression is associated with reduced chromatin contacts within the topologically associating domains. Unexpectedly, Myod1Cre-driven deletion of Sox11 in embryonic myoblasts has no effects on muscle development and growth, resulting in apparently healthy muscles that regenerate normally. Pax7CreER- or Rosa26CreER- driven (MuSC-specific or global) deletion of Sox11 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 remains to be elucidated. The online version contains supplementary material available at 10.1186/s13395-023-00324-0.
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