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Here, we describe a multilayered omics approach to dissect adipose progenitor cell heterogeneity in three dimensions: progenitor subpopulation, sex, and anatomical localization. We applied state-of-the-art mass spectrometry methods to quantify proteins in eight different stromal cell populations from perigonadal and inguinal WAT of male and female mice and acquired transcript expression levels of genes using RNA-seq. Our data unveil molecular signatures defining sex differences in preadipocyte differentiation and identify regulatory pathways that functionally distinguish adipose progenitor subpopulations.

Adipose tissue is exceptional in its ability to adapt to changes in physiological, pathophysiological, and environmental conditions. The condition of obesity highlights an unparalleled capacity of white adipose tissue WAT to expand in size in the face of positive energy balance. This adaption to increased demand for energy storage is critical in order to maintain adequate lipid storage in WAT rather than deleterious ectopic lipid deposition in non-adipose tissues Hepler and Gupta, WAT expansion in obesity occurs in a sex- and region-dependent manner Karastergiou et al.

Preferential expansion of gluteo-femoral subcutaneous WAT depots, often observed in females, is associated with protection against metabolic abnormalities Lotta et al.