Bareja Akshay, Holt Jason A, Luo Guizhen, Chang Calvin, Lin Junyu, Hinken Aaron C, Freudenberg Johannes M, Kraus William E, Evans William J, Billin Andrew N
Department of Medicine, Duke University, Durham, North Carolina, United States of America ; Muscle Metabolism Discovery Performance Unit, Metabolic Pathways and Cardiovascular Therapeutic Area, GlaxoSmithKline, Research Triangle Park, North Carolina, United States of America.
Muscle Metabolism Discovery Performance Unit, Metabolic Pathways and Cardiovascular Therapeutic Area, GlaxoSmithKline, Research Triangle Park, North Carolina, United States of America.
PLoS One. 2014 Feb 28;9(2):e90398. doi: 10.1371/journal.pone.0090398. eCollection 2014.
Satellite cells are the chief contributor to skeletal muscle growth and regeneration. The study of mouse satellite cells has accelerated in recent years due to technical advancements in the isolation of these cells. The study of human satellite cells has lagged and thus little is known about how the biology of mouse and human satellite cells compare. We developed a flow cytometry-based method to prospectively isolate human skeletal muscle progenitors from the satellite cell pool using positive and negative selection markers. Results show that this pool is enriched in PAX7 expressing cells that possess robust myogenic potential including the ability to give rise to de novo muscle in vivo. We compared mouse and human satellite cells in culture and identify differences in the elaboration of the myogenic genetic program and in the sensitivity of the cells to cytokine stimulation. These results indicate that not all mechanisms regulating mouse satellite cell activation are conserved in human satellite cells and that such differences may impact the clinical translation of therapeutics validated in mouse models. Thus, the findings of this study are relevant to developing therapies to combat muscle disease.
卫星细胞是骨骼肌生长和再生的主要贡献者。近年来，由于这些细胞分离技术的进步，对小鼠卫星细胞的研究加速了。对人类卫星细胞的研究滞后，因此对小鼠和人类卫星细胞的生物学特性如何比较知之甚少。我们开发了一种基于流式细胞术的方法，使用阳性和阴性选择标记物从卫星细胞池中前瞻性地分离人类骨骼肌祖细胞。结果表明，该细胞池富含表达PAX7的细胞，这些细胞具有强大的成肌潜力，包括在体内产生新生肌肉的能力。我们比较了培养中的小鼠和人类卫星细胞，确定了成肌遗传程序的阐述以及细胞对细胞因子刺激的敏感性方面的差异。这些结果表明，并非所有调节小鼠卫星细胞激活的机制在人类卫星细胞中都是保守的，而且这些差异可能会影响在小鼠模型中验证的治疗方法的临床转化。因此，本研究的结果与开发对抗肌肉疾病的疗法相关。
