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

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.