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 Pax7FAPs. 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 Pax7FAPs persist into adulthood. Furthermore, adult muscle injury triggered de novo generation of Pax7FAPs, which exhibited higher proliferative capacity than resident stromal cells. This postnatal Pax7+ multipotency reveals an additional cellular contribution to muscle development and regeneration.