Pasut Alessandra, Chang Natasha C, Gurriaran-Rodriguez Uxia, Faulkes Sharlene, Yin Hang, Lacaria Melanie, Ming Hong, Rudnicki Michael A
Sprott Center for Stem Cell Research, Ottawa Hospital Research Institute, Ottawa, ON K1H8L6, Canada; Department of Cellular and Molecular Medicine, Faculty of Medicine, University of Ottawa, Ottawa, ON K1H8M5, Canada.
Sprott Center for Stem Cell Research, Ottawa Hospital Research Institute, Ottawa, ON K1H8L6, Canada.
Cell Rep. 2016 Jul 12;16(2):333-343. doi: 10.1016/j.celrep.2016.06.001. Epub 2016 Jun 23.
Pax7 is a nodal transcription factor that is essential for regulating the maintenance, expansion, and myogenic identity of satellite cells during both neonatal and adult myogenesis. Deletion of Pax7 results in loss of satellite cells and impaired muscle regeneration. Here, we show that ectopic expression of the constitutively active intracellular domain of Notch1 (NICD1) rescues the loss of Pax7-deficient satellite cells and restores their proliferative potential. Strikingly NICD1-expressing satellite cells do not undergo myogenic differentiation and instead acquire a brown adipogenic fate both in vivo and in vitro. NICD-expressing Pax7(-/-) satellite cells fail to upregulate MyoD and instead express the brown adipogenic marker PRDM16. Overall, these results show that Notch1 activation compensates for the loss of Pax7 in the quiescent state and acts as a molecular switch to promote brown adipogenesis in adult skeletal muscle.
Pax7是一种关键转录因子，对于在新生儿和成体肌生成过程中调节卫星细胞的维持、增殖以及肌源性特性至关重要。Pax7的缺失会导致卫星细胞丧失以及肌肉再生受损。在此，我们表明，Notch1组成型激活的胞内结构域（NICD1）的异位表达挽救了Pax7缺陷型卫星细胞的丧失，并恢复了它们的增殖潜能。引人注目的是，表达NICD1的卫星细胞不会发生肌源性分化，而是在体内和体外都获得了棕色脂肪生成命运。表达NICD的Pax7(-/-)卫星细胞无法上调MyoD，而是表达棕色脂肪生成标志物PRDM16。总体而言，这些结果表明，Notch1激活在静止状态下补偿了Pax7的缺失，并作为一种分子开关促进成体骨骼肌中的棕色脂肪生成。
