Myogenic potential, survival and expansion of mammalian muscle progenitors depend on the myogenic determinants Pax3 and Pax7 embryonically 1 , and Pax7 alone perinatally 2 - 5. Several in vitro studies support Pax7's critical role in these functions of adult muscle stem cells 5 - 8 , i. Surprisingly, dual adult inactivation of Pax3 and Pax7 also results in normal muscle regeneration. Multiple time points of gene inactivation reveal Pax7 is only required up to the juvenile period when progenitor cells transition into quiescence. We further demonstrate a cell intrinsic difference between neonatal progenitor and adult satellite cells in their Pax7 -dependency. Our finding of an age-dependent change in the genetic requirement for muscle stem cells cautions against inferring adult stem cell biology from embryonic studies, and has direct implications for the use of stem cells from hosts of different ages in transplantation-based therapy.
Analysis of human satellite cell dynamics on cultured adult skeletal muscle myofibers
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Adult stem cells are important for tissue maintenance and repair. One key question is how such cells are specified and then protected from differentiation for a prolonged period. Through activity of the Notch pathway, a subset of MPs produce an alternate zfh1-short isoform, which lacks the miR-8 seed site. Zfh1 protein is thus maintained in these cells, enabling them to escape differentiation and persist as MPs in the adult. There, like mammalian satellite cells, they contribute to muscle homeostasis.
Adult satellite cells and embryonic muscle progenitors have distinct genetic requirements
Myogenic potential, survival and expansion of mammalian muscle progenitors depend on the myogenic determinants Pax3 and Pax7 embryonically, and Pax7 alone perinatally. Several in vitro studies support the critical role of Pax7 in these functions of adult muscle stem cells satellite cells , but a formal demonstration has been lacking in vivo. Dual adult inactivation of Pax3 and Pax7 also results in normal muscle regeneration.
Metrics details. Maintaining stem cells in physiologically relevant states is necessary to understand cell and context-specific signalling paradigms and to understand complex interfaces between cells in situ. Understanding human stem cell function is largely based on tissue biopsies, cell culture, and transplantation into model organisms.