Department of Physiology and Cell Biology, The Ohio State University, Columbus, OH, USA.
Seraxis Inc, Germantown, MD, USA.
Stem Cell Reports. 2021 Dec 14;16(12):2913-2927. doi: 10.1016/j.stemcr.2021.10.006. Epub 2021 Nov 4.
Skeletal muscle stem cells, i.e., satellite cells (SCs), are the essential source of new myonuclei for skeletal muscle regeneration following injury or chronic degenerative myopathies. Both SC number and regenerative capacity diminish during aging. However, molecular regulators that govern sizing of the initial SC pool are unknown. We demonstrate that fibroblast growth factor 6 (FGF6) is critical for SC pool scaling. Mice lacking FGF6 have reduced SCs of early postnatal origin and impaired regeneration. By contrast, increasing FGF6 during the early postnatal period is sufficient for SC expansion. Together, these data support that FGF6 is necessary and sufficient to modulate SC numbers during a critical postnatal period to establish the quiescent adult muscle stem cell pool. Our work highlights postnatal development as a time window receptive for scaling a somatic stem cell population via growth factor signaling, which might be relevant for designing new biomedical strategies to enhance tissue regeneration.
骨骼肌干细胞，即卫星细胞 (SCs)，是损伤或慢性退行性肌病后骨骼肌再生的新肌核的重要来源。SC 数量和再生能力在衰老过程中都会下降。然而，控制初始 SC 池大小的分子调节剂尚不清楚。我们证明，成纤维细胞生长因子 6 (FGF6) 对于 SC 池缩放至关重要。缺乏 FGF6 的小鼠具有减少的早期出生后起源的 SC 和受损的再生。相比之下，在出生后的早期阶段增加 FGF6 足以促进 SC 扩增。这些数据共同支持 FGF6 在关键的出生后时期是调节 SC 数量以建立静止的成年肌肉干细胞池所必需和充分的。我们的工作强调了出生后发育作为通过生长因子信号对体细胞干细胞群体进行缩放的时间窗口，这对于设计新的生物医学策略以增强组织再生可能是相关的。
