Comparative single-cell lineage tracing identifies distinct adipocyte precursor dynamics in skin and inguinal fat

White adipose tissue supports essential physiological functions through adipocyte precursor cells (APCs), comprising progenitors and preadipocytes, which generate mature adipocytes during depot expansion. Using single-cell RNA sequencing-based lineage tracing, we characterize APCs in skin adipose tissue—a depot uniquely capable of rapid adipogenesis compared with other sites, such as inguinal adipose. We identify a previously uncharacterized population of immature preadipocytes and reveal distinct differentiation potentials among APCs. Contrary to traditional stepwise differentiation models, progenitors predominantly generate committed preadipocytes, whereas preexisting preadipocytes accumulate in immature states with divergent potential. Leveraging this refined APC hierarchy, we uncover Sox9 as a crucial regulator of progenitor proliferation and adipogenic differentiation. Cross-depot transplantation further demonstrates how intrinsic and extrinsic factors differentially regulate skin progenitor behavior, highlighting distinct adipogenic dynamics between skin and inguinal depots. Together, these insights redefine the cellular hierarchy and molecular mechanisms underpinning rapid adipogenesis in skin adipose tissue. • Skin adipocyte precursors differentiate via multiple parallel trajectories • Progenitors and preadipocytes exhibit distinct lineage dynamics • Sox9 critically regulates skin adipocyte progenitor differentiation • Skin adipogenesis is uniquely regulated compared with other adipose depots Morris and colleagues use single-cell lineage tracing to track adipocyte formation in mouse skin. They demonstrate that distinct precursor populations—progenitors and immature preadipocytes—exhibit different potentials for generating mature adipocytes, uncover depot-specific extrinsic regulation, and identify Sox9 as a key intrinsic regulator of skin adipogenesis.