Liu Ning, Garry Glynnis A, Li Stephen, Bezprozvannaya Svetlana, Sanchez-Ortiz Efrain, Chen Beibei, Shelton John M, Jaichander Priscilla, Bassel-Duby Rhonda, Olson Eric N
Department of Molecular Biology, Hamon Center for Regenerative Science and Medicine, Sen. Paul D. Wellstone Muscular Dystrophy Cooperative Research Center, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, Texas 75390, USA.
Department of Clinical Sciences, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, Texas 75390, USA.
Nat Cell Biol. 2017 Mar;19(3):202-213. doi: 10.1038/ncb3477. Epub 2017 Feb 20.
Skeletal muscle possesses remarkable regenerative potential due to satellite cells, an injury-responsive stem cell population located beneath the muscle basal lamina that expresses Pax7. By lineage tracing of progenitor cells expressing the Twist2 (Tw2) transcription factor in mice, we discovered a myogenic lineage that resides outside the basal lamina of adult skeletal muscle. Tw2 progenitors are molecularly and anatomically distinct from satellite cells, are highly myogenic in vitro, and can fuse with themselves and with satellite cells. Tw2 progenitors contribute specifically to type IIb/x myofibres during adulthood and muscle regeneration, and their genetic ablation causes wasting of type IIb myofibres. We show that Tw2 expression maintains progenitor cells in an undifferentiated state that is poised to initiate myogenesis in response to appropriate cues that extinguish Tw2 expression. Tw2-expressing myogenic progenitors represent a previously unrecognized, fibre-type-specific stem cell involved in postnatal muscle growth and regeneration.
由于卫星细胞的存在，骨骼肌具有显著的再生潜力。卫星细胞是位于肌肉基膜下方的一群损伤反应性干细胞，表达Pax7。通过对小鼠中表达Twist2（Tw2）转录因子的祖细胞进行谱系追踪，我们发现了一个位于成年骨骼肌基膜外的生肌谱系。Tw2祖细胞在分子和解剖学上与卫星细胞不同，在体外具有高度生肌能力，并且可以与自身以及卫星细胞融合。在成年期和肌肉再生过程中，Tw2祖细胞特异性地贡献于IIb/x型肌纤维，它们的基因消融会导致IIb型肌纤维萎缩。我们表明，Tw2的表达使祖细胞维持在未分化状态，这种状态准备好在消除Tw2表达的适当信号的作用下启动肌生成。表达Tw2的生肌祖细胞代表了一种以前未被认识的、参与出生后肌肉生长和再生的纤维类型特异性干细胞。
