Tbx1 regulates inherited metabolic and myogenic abilities of progenitor cells derived from slow- and fast-type muscle
Tbx1 regulates inherited metabolic and myogenic abilities of progenitor cells derived from slow- and fast-type muscle
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DOI：
10.1038/s41418-018-0186-4
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发表时间：
2019-06-01
影响因子：
12.4
通讯作者：
Shigemoto, Kazuhiro
中科院分区：
文献类型：
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作者：
Motohashi, Norio;Uezumi, Akiyoshi;Shigemoto, Kazuhiro
骨骼肌分为慢型和快型肌肉，它们具有不同的收缩和代谢特性。已知与每种肌纤维类型相关的肌源性祖细胞在胚胎发育期间内在地致力于特定的肌纤维谱系。然而，目前还不清楚是否出生后的成年肌源性细胞的功能是归因于它们所在的肌纤维，以及是否来自慢型和快型纤维的肌源性细胞的特征可以在遗传水平上区分。在这项研究中，我们分别从慢型和快型肌肉中分离出成体卫星细胞，并观察到来自每种类型肌肉的卫星细胞产生表达与其原始肌肉相似的肌球蛋白重链异构体的肌管，并显示出不同的代谢特征。值得注意的是，我们发现与快速肌肉来源的细胞相比，慢速肌肉来源的细胞分化潜力低，但自我更新潜力高。此外，将慢肌源性细胞移植到快型肌肉中的细胞移植实验表明，慢肌源性细胞比快肌源性细胞更有助于肌纤维形成和卫星细胞构成，这表明受体肌纤维类型可能不会影响肌原性细胞的预定能力。基因表达分析确定T-box转录因子Tbx 1作为一个高表达的基因在快速肌源性成肌细胞。获得和功能丧失的实验表明，Tbx 1调制肌纤维类型和肌管中的氧化代谢，Tbx 1刺激成肌细胞分化，但不调节肌细胞自我更新。我们的数据表明，成肌祖细胞的代谢和成肌特性取决于它们所来源的肌肉类型，并且Tbx 1表达部分解释了来自快型和慢型肌肉的成肌细胞的功能差异。
Skeletal muscle is divided into slow- and fast-type muscles, which possess distinct contractile and metabolic properties. Myogenic progenitors associated with each muscle fiber type are known to intrinsically commit to specific muscle fiber lineage during embryonic development. However, it is still unclear whether the functionality of postnatal adult myogenic cells is attributable to the muscle fiber in which they reside, and whether the characteristics of myogenic cells derived from slow- and fast-type fibers can be distinguished at the genetic level. In this study, we isolated adult satellite cells from slow and fast-type muscle individually and observed that satellite cells from each type of muscle generated myotubes expressing myosin heavy chain isoforms similar to their original muscle, and showed different metabolic features. Notably, we discovered that slow muscle-derived cells had low potential to differentiate but high potential to self-renew compared with fast muscle-derived cells. Additionally, cell transplantation experiments of slow muscle-derived cells into fast-type muscle revealed that slow muscle-derived cells could better contribute to myofiber formation and satellite cell constitution than fast muscle-derived cells, suggesting that the recipient muscle fiber type may not affect the predetermined abilities of myogenic cells. Gene expression analyses identified T-box transcriptional factor Tbx1 as a highly expressed gene in fast muscle-derived myoblasts. Gain- and loss-of-function experiments revealed that Tbx1 modulated muscle fiber types and oxidative metabolism in myotubes, and that Tbx1 stimulated myoblast differentiation, but did not regulate myogenic cell self-renewal. Our data suggest that metabolic and myogenic properties of myogenic progenitor cells vary depending on the type of muscle from which they originate, and that Tbx1 expression partially explains the functional differences of myogenic cells derived from fast-type and slow-type muscles.