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The Molecular Regulation of Muscle Stem Cell Function

机译:肌肉干细胞功能的分子调节

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Muscle satellite cells are responsible for the postnatal growth and robust regeneration capacity of adult skeletal muscle. A sub-set of satellite cells purified from adult skeletal muscle is capable of repopulating the satellite cell pool, suggesting that it hasdirect therapeutic potential for treating degenerative muscle disease. Satellite cells uniformly express the transcription factorPax7, and Pax7 is required for satellite cell viability and to give rise to myogenic precursors that express the basic helix-loop-helic (bHLH) transcription factors Myf5 and MyoD. Pax7 activates expression of target genes such as My/5 and MyoDthrough recruitment of the WdrS/Ash2L/MLL2 histone methyltransferase complex. Extensive genetic analysis has revealedthat Myf5 and MyoD are required for myogenic determination, whereas myogenin and MRF4 have roles in terminal differ-entiation. Using a Myf5-Cre knockin allele and an R26R-YFP Cre reporter, we observed that in vivo about 10% of satellitecells only express Pax7 and have never expressed Myf5. Moreover, we found that Pax7'/Myf5 satellite cells give rise toPax7~+/Myf5~+ satellite cells through basal-apical asymmetric cell divisions. Therefore, satellite cells in skeletal muscle are aheterogeneous population composed of satellite stem cells (Pax7/Myf5-) and satellite myogenic cells (Pax7/Myf5).Evidence is accumulating that indicates that satellite stem cells represent a true stem cell reservoir, and targeting mechanismsthat regulate their function represents an important therapeutic strategy for the treatment of neuromuscular disease.
机译:肌卫星细胞负责成人骨骼肌的后生长和鲁棒再生能力。从成年骨骼肌纯化的卫星细胞的亚卫星细胞能够重新灌注卫星电池池,这表明它具有治疗退行性肌肉疾病的治疗潜力。卫星细胞均匀地表达转录因子β7,并且Pax7是卫星细胞活力所必需的,并产生表达基本螺旋环 - 螺旋(BHLH)转录因子MyF5和Myod的肌原遗传学前体。 PAX7激活靶基因的表达,例如MY / 5和MyodeDhrough的WDR / ASH2L / MLL2组蛋白甲基转移酶复合物的募集。广泛的遗传分析揭示了MyF5和MyOD对于肌原测定需要,而Myogenin和MRF4在终端不同的位置具有作用。使用MYF5-CRE Knockin等位基因和R26R-YFP CRE记者,我们观察到,在体内约10%的卫星只需表达PAX7并且从未表达过MYF5。此外,我们发现PAX7'/ MYF5卫星电池通过基底 - 顶端不对称细胞分区给出Topax7〜+ / myF5〜+卫星细胞。因此,骨骼肌中的卫星细胞是由卫星干细胞(PAX7 / MYF5-)和卫星肌原细胞组成的含有偶联的群体(PAX7 / MYF5)。累积,表明卫星干细胞代表真正的干细胞储层和靶向机制调节其功能是治疗神经血型疾病的重要治疗策略。

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