Department of Applied Human Sciences, University of Prince Edward Island, Charlottetown, Prince Edward Island, Canada.
Department of Medical Neuroscience, Dalhousie University, Halifax, Nova Scotia, Canada.
FASEB J. 2022 Dec;36(12):e22642. doi: 10.1096/fj.202201349RR.
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.
骨骼肌由亚层、表达 Pax7 的卫星细胞维持和修复。然而，最近的小鼠研究描述了另一种存在于肌纤维间质中并表达转录因子 Twist2 的成肌前体细胞群。Twist2 表达细胞专门修复和维持 IIx/b 型肌纤维。目前，尚不清楚 Twist2 表达细胞是否存在于人类骨骼肌中，以及它们是否作为成肌前体细胞发挥作用。在这里，我们结合单细胞 RNA 测序分析和免疫荧光染色来证明 Twist2 表达细胞在人类骨骼肌中的身份和定位。发现 Twist2 表达细胞在解剖学和转录上与纤维脂肪祖细胞 (FAP) 相当，并且缺乏典型的卫星细胞标志物如 Pax7 的表达。比较分析表明，人类和小鼠的 Twist2 表达细胞在转录上高度相似，并且在体内位于相同的解剖结构中。对年轻和老年骨骼肌活检样本的检查表明，Twist2 阳性细胞在老年肌肉中更为普遍，并在人类进行 12 周的抗阻训练 (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，并且它们的丰度令人惊讶地与 RET 后的 CSA 和肌核域大小呈负相关。总之，我们已经在人类骨骼肌中鉴定出表达 Twist2 的细胞，这些细胞对衰老和运动有反应。进一步研究它们的成肌潜能是值得的。
