All data generated or analysed during this study are included in the manuscript and supporting files. 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.
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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. Such preferential regulation of a specific RNA isoform, with differential sensitivity to miRs, is a powerful mechanism for maintaining a population of poised progenitors and may be of widespread significance. Growth and regeneration of adult tissues depends on stem cells, which remain undifferentiated while retaining the potential to generate differentiated progeny.
Pervasive satellite cell contribution to uninjured adult muscle fibers
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.
Metrics details. Adult skeletal muscle adapts to functional needs, maintaining consistent numbers of myonuclei and stem cells. Although resident muscle stem cells or satellite cells are required for muscle growth and repair, in uninjured muscle, these cells appear quiescent and metabolically inactive. Satellite cells contribute to uninjured myofibers either following a cell division or directly without an intervening cell division. The frequency of satellite cell fusion into the skeletal muscle fibers is greater than previously estimated, suggesting an important functional role for satellite cell fusion into adult myofibers and a requirement for active maintenance of satellite cell numbers in uninjured skeletal muscle.