San Raffaele Telethon Institute for Gene Therapy (HSR-TIGET), San Raffaele Scientific Institute, Milan, Italy.
Stem Cells. 2010 May;28(5):965-73. doi: 10.1002/stem.418.
Several reports showed that hematopoietic stem cells (HSCs) participate in muscle regeneration, raising hope for their therapeutic potential for degenerative muscle diseases. However, proof that HSCs are able to reprogram their fate and enter a myogenic pathway, remains elusive. We demonstrate that murine bone marrow (BM)-derived hematopoietic cells, carrying reporter genes controlled by muscle-specific regulatory elements from the Myf5, myosin light chain (MLC3F), or MCK genes, are induced by myoblasts to activate muscle-specific genes. This potential resides in the more undifferentiated progenitors, expressing surface markers typical of HSCs. Comparative gene expression profiling of CD45(+)/Sca1(+) cells isolated from muscle or BM shows that hematopoietic cells participate to muscle regeneration, by undergoing a profound although incomplete myogenic reprogramming on interaction with the muscle microenviroment. These cells undergo specification and differentiation independently from Pax7 and MyoD, and lack Pax7-associated properties, such as self-renewal and proliferation, distinguishing from satellite cells. Our findings indicate that hematopoietic cells, on seeding in the muscle, become a distinct cell population endowed with myogenic potential.
有几项报告表明，造血干细胞（HSCs）参与肌肉再生，这为它们治疗退行性肌肉疾病的潜力带来了希望。然而，造血干细胞能够重新编程其命运并进入肌源性途径的证据仍然难以捉摸。我们证明，携带由 Myf5、肌球蛋白轻链（MLC3F）或 MCK 基因的肌肉特异性调节元件控制的报告基因的鼠骨髓（BM）来源的造血细胞，可被成肌细胞诱导以激活肌肉特异性基因。这种潜力存在于更未分化的祖细胞中，这些祖细胞表达典型的造血干细胞表面标志物。从肌肉或 BM 分离的 CD45(+)/Sca1(+)细胞的比较基因表达谱表明，造血细胞通过与肌肉微环境相互作用，经历深刻但不完全的肌源性重编程，参与肌肉再生。这些细胞在与 Pax7 和 MyoD 相互作用时独立于 Pax7 和 MyoD 进行特化和分化，并且缺乏 Pax7 相关特性，例如自我更新和增殖，与卫星细胞区分开来。我们的研究结果表明，造血细胞在播种到肌肉中后，成为具有成肌潜能的独特细胞群体。
