Massachusetts General Hospital, Center of Regenerative Medicine, Harvard University, Boston, MA 02114, USA.
Cell Stem Cell. 2010 Feb 5;6(2):117-29. doi: 10.1016/j.stem.2009.12.015.
Satellite cells are skeletal muscle stem cells capable of self-renewal and differentiation after transplantation, but whether they contribute to endogenous muscle fiber repair has been unclear. The transcription factor Pax7 marks satellite cells and is critical for establishing the adult satellite cell pool. By using a lineage tracing approach, we show that after injury, quiescent adult Pax7(+) cells enter the cell cycle; a subpopulation returns to quiescence to replenish the satellite cell compartment, while others contribute to muscle fiber formation. We demonstrate that Sprouty1 (Spry1), a receptor tyrosine kinase signaling inhibitor, is expressed in quiescent Pax7(+) satellite cells in uninjured muscle, downregulated in proliferating myogenic cells after injury, and reinduced as Pax7(+) cells re-enter quiescence. We show that Spry1 is required for the return to quiescence and homeostasis of the satellite cell pool during repair. Our results therefore define a role for Spry1 in adult muscle stem cell biology and tissue repair.
卫星细胞是骨骼肌干细胞，在移植后能够自我更新和分化，但它们是否有助于内源性肌纤维修复尚不清楚。转录因子 Pax7 标记卫星细胞，对于建立成体卫星细胞池至关重要。通过使用谱系追踪方法，我们表明，损伤后，静止的成年 Pax7(+)细胞进入细胞周期；亚群返回静止状态以补充卫星细胞池，而其他细胞则有助于肌纤维形成。我们证明，受体酪氨酸激酶信号抑制剂 Sprouty1 (Spry1) 在未受伤肌肉中的静止 Pax7(+)卫星细胞中表达，在受伤后增殖的成肌细胞中下调，并在 Pax7(+)细胞重新进入静止状态时重新诱导表达。我们表明 Spry1 是修复过程中卫星细胞池恢复静止和维持平衡所必需的。因此，我们的研究结果定义了 Spry1 在成体肌肉干细胞生物学和组织修复中的作用。
