骨骼肌卫星细胞中的Pax7与成肌进程
Pax7 and myogenic progression in skeletal muscle satellite cells.
作者信息
Zammit Peter S, Relaix Frederic, Nagata Yosuke, Ruiz Ana Pérez, Collins Charlotte A, Partridge Terence A, Beauchamp Jonathan R
机构信息
Muscle Cell Biology Group, Medical Research Council Clinical Sciences Centre, Imperial College London, Hammersmith Hospital Campus, Du Cane Road, London, W12 0NN, UK.
出版信息
J Cell Sci. 2006 May 1;119(Pt 9):1824-32. doi: 10.1242/jcs.02908. Epub 2006 Apr 11.
Skeletal muscle growth and regeneration are attributed to satellite cells - muscle stem cells resident beneath the basal lamina that surrounds each myofibre. Quiescent satellite cells express the transcription factor Pax7 and when activated, coexpress Pax7 with MyoD. Most then proliferate, downregulate Pax7 and differentiate. By contrast, others maintain Pax7 but lose MyoD and return to a state resembling quiescence. Here we show that Pax7 is able to drive transcription in quiescent and activated satellite cells, and continues to do so in those cells that subsequently cease proliferation and withdraw from immediate differentiation. We found that constitutive expression of Pax7 in satellite-cell-derived myoblasts did not affect MyoD expression or proliferation. Although maintained expression of Pax7 delayed the onset of myogenin expression it did not prevent, and was compatible with, myogenic differentiation. Constitutive Pax7 expression in a Pax7-null C2C12 subclone increased the proportion of cells expressing MyoD, showing that Pax7 can act genetically upstream of MyoD. However these Pax7-null cells were unable to differentiate into normal myotubes in the presence of Pax7. Therefore Pax7 may be involved in maintaining proliferation and preventing precocious differentiation, but does not promote quiescence.
骨骼肌的生长和再生归因于卫星细胞——位于围绕每条肌纤维的基膜下方的肌肉干细胞。静止的卫星细胞表达转录因子Pax7,激活后,与MyoD共同表达Pax7。大多数卫星细胞随后增殖,下调Pax7并分化。相比之下,其他卫星细胞则维持Pax7表达,但失去MyoD并恢复到类似静止的状态。在此,我们表明Pax7能够在静止和激活的卫星细胞中驱动转录,并在随后停止增殖并退出直接分化的细胞中继续驱动转录。我们发现,在卫星细胞来源的成肌细胞中组成性表达Pax7不会影响MyoD表达或增殖。尽管持续表达Pax7会延迟肌生成素表达的开始,但它并不阻止肌源性分化,且与肌源性分化相容。在Pax7基因缺失的C2C12亚克隆中组成性表达Pax7会增加表达MyoD的细胞比例,表明Pax7在基因上可作用于MyoD的上游。然而,在存在Pax7的情况下,这些Pax7基因缺失的细胞无法分化为正常的肌管。因此,Pax7可能参与维持增殖并防止过早分化,但不促进静止。