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A Pax3/Pax7-dependent population of skeletal muscle progenitor cells

机译:Pax3 / Pax7依赖性骨骼肌祖细胞群

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During vertebrate development, successive phases of embryonic and fetal myogenesis lead to the formation and growth of skeletal muscles(1). Although the origin and molecular regulation of the earliest embryonic muscle cells is well understood(2), less is known about later stages of myogenesis. We have identified a new cell population that expresses the transcription factors Pax3 and Pax7 (paired box proteins 3 and 7) but no skeletal-muscle-specific markers. These cells are maintained as a proliferating population in embryonic and fetal muscles of the trunk and limbs throughout development. Using a stable green fluorescent protein (GFP) reporter targeted to Pax3, we demonstrate that they constitute resident muscle progenitor cells that subsequently become myogenic and form skeletal muscle. Late in fetal development, these cells adopt a satellite cell position characteristic of progenitor cells in postnatal muscle. In the absence of both Pax3 and Pax7, further muscle development is arrested and only the early embryonic muscle of the myotome forms. Cells failing to express Pax3 or Pax7 die or assume a non-myogenic fate. We conclude that this resident Pax3/Pax7-dependent progenitor cell population constitutes a source of myogenic cells of prime importance for skeletal muscle formation, a finding also of potential value in the context of cell therapy for muscle disease.
机译:在脊椎动物发育过程中,胚胎和胎儿肌生成的连续阶段导致骨骼肌的形成和生长(1)。尽管人们对最早的胚胎肌肉细胞的起源和分子调控的理解是众所周知的(2),但对于成肌的后期阶段却知之甚少。我们已经确定了一个新的细胞群,该细胞群可以表达转录因子Pax3和Pax7(配对框蛋白3和7),但是没有骨骼肌特异性标记。在整个发育过程中,这些细胞在躯干和四肢的胚胎和胎儿肌肉中作为增殖种群得以维持。使用针对Pax3的稳定的绿色荧光蛋白(GFP)报告基因,我们证明了它们构成了常驻的肌肉祖细胞,随后变成了成肌细胞并形成了骨骼肌。在胎儿发育后期,这些细胞采用出生后肌肉中祖细胞特征性的卫星细胞位置。在Pax3和Pax7都不存在的情况下,进一步的肌肉发育被阻止,仅形成了子宫肌瘤的早期胚胎肌肉。无法表达Pax3或Pax7的细胞死亡或承担非肌原性命运。我们得出的结论是,该常驻Pax3 / Pax7依赖的祖细胞群构成了对骨骼肌形成至关重要的成肌细胞来源,这一发现在针对肌肉疾病的细胞疗法中也具有潜在价值。

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