Abstract：
Skeletal muscle is maintained and repaired by sub-laminar, Pax7-expressing satellite cells. However, recent mouse investigations have described a second myogenic progenitor population that resides within the myofiber interstitium and expresses the transcription factor Twist2. Twist2-expressing cells exclusively repair and maintain type IIx/b muscle fibers. Currently, it is unknown if Twist2-expressing cells are present in human skeletal muscle and if they function as myogenic progenitors. Here, we perform a combination of single-cell RNA sequencing analysis and immunofluorescence staining to demonstrate the identity and localization of Twist2-expressing cells in human skeletal muscle. Twist2-expressing cells were identified to be anatomically and transcriptionally comparable to fibro-adipogenic progenitors (FAPs) and lack expression of typical satellite cell markers such as Pax7. Comparative analysis revealed that human and mouse Twist2-expressing cells were highly transcriptionally analogous and resided within the same anatomical structures in vivo. Examination of young and aged skeletal muscle biopsy samples revealed that Twist2-positive cells are more prevalent in aged muscle and increase following 12-weeks of resistance exercise training (RET) in humans. However, the quantity of Twist2-positive cells was not correlated with indices of muscle mass or muscle fiber cross-sectional area (CSA) in young or older muscle, and their abundance was surprisingly, negatively correlated with CSA and myonuclear domain size following RET. Taken together, we have identified cells expressing Twist2 in human skeletal muscle which are responsive to aging and exercise. Further examination of their myogenic potential is warranted.
摘要：
骨骼肌由层下层维持和修复，表达Pax7的卫星细胞。然而,最近的小鼠研究描述了第二个肌源性祖细胞群，它位于肌纤维间质内并表达转录因子Twist2。Twist2表达细胞专门修复和维持IIx/b型肌纤维。目前,目前尚不清楚Twist2表达细胞是否存在于人类骨骼肌中，以及它们是否充当肌原祖细胞。这里,我们进行了单细胞RNA测序分析和免疫荧光染色的组合,以证明人骨骼肌中Twist2表达细胞的身份和定位.表达Twist2的细胞被鉴定为在解剖学和转录上与纤维脂肪原祖细胞(FAP)相当,并且缺乏典型的卫星细胞标志物如Pax7的表达。比较分析显示，人和小鼠Twist2表达细胞在转录上高度相似，并在体内位于相同的解剖结构内。对年轻和老年骨骼肌活检样本的检查显示，Twist2阳性细胞在老年肌肉中更为普遍，并且在人类进行12周的抗阻运动训练（RET）后增加。然而,Twist2阳性细胞的数量与年轻或老年肌肉的肌肉质量或肌纤维横截面积（CSA）指数无关，他们的丰富令人惊讶，RET后与CSA和肌核结构域大小呈负相关。一起来看,我们已经确定了在人类骨骼肌中表达Twist2的细胞，这些细胞对衰老和运动有反应。需要进一步检查它们的生肌潜能。
