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

Organs comprise diverse cell types originating from shared or distinct lineages. During embryogenesis, mesodermal Pax7⁺ progenitors give rise to skeletal muscle as well as non-muscle lineages like dermis and adipocytes. Here, we asked whether Pax7⁺ cells retain multipotency during early postnatal limb muscle growth. Lineage tracing in neonatal mice revealed unexpected early postnatal plasticity, yielding multiple non-myogenic lineages, including a previously unrecognized subpopulation of fibro-adipogenic progenitors, termed Pax7^FAPs. Using mouse models, we demonstrated that Notch signaling primes neonatal Pax7⁺ cells toward a fibrogenic molecular identity, biasing their trajectory away from myogenesis. Long-term tracing confirmed that neonatally generated Pax7^FAPs persist into adulthood. Furthermore, adult muscle injury triggered de novo generation of Pax7^FAPs, which exhibited higher proliferative capacity than resident stromal cells. This postnatal Pax7⁺ multipotency reveals an additional cellular contribution to muscle development and regeneration.