Postnatal Pax7-expressing limb cells are multipotent and generate non-myogenic lineages that persist into adulthood.

Organs are composed of diverse cell types that arise from distinct or shared progenitor cells. Skeletal muscle originates from mesoderm-derived Pax7⁺ stem/progenitor cells, which typically differentiate into myoblasts and form muscle fibers. During embryonic development, however, Pax7⁺ somitic cells can also generate non-muscle lineages such as dermis and adipocytes.In this study, we examined whether Pax7⁺ cells in postnatal growing limb muscle retain similar multipotency. Lineage-tracing analyses revealed unexpected plasticity during the early postnatal period, with Pax7⁺ cells giving rise not only to myogenic cells but also to multiple non-myogenic lineages. Among these, we identified a previously unrecognized Pax7-derived fibro-adipogenic progenitor population (Pax7FAPs). Using mouse models, we further found that Notch signaling promotes a fibrogenic molecular program in neonatal Pax7⁺ cells, at the expense of myogenic differentiation, potentially biasing their fate toward the Pax7FAP lineage. Long-term tracing showed that Pax7-derived FAPs generated during the neonatal stage persist into adulthood and display enhanced proliferative capacity following muscle injury. Moreover, adult muscle injury can also induce the generation of Pax7FAPs, which proliferate more robustly than resident stromal cells. Together, these findings reveal previously unappreciated multipotency in postnatal Pax7⁺ cells and provide new insights into their contribution to muscle development and regeneration.