Oprescu Stephanie N, Baumann Nick, Chen Xiyue, Sun Qiang, Zhao Yu, Yue Feng, Wang Huating, Kuang Shihuan
bioRxiv. 2023 Mar 31:2023.03.30.534956. doi: 10.1101/2023.03.30.534956.
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.
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。