Distinct Functional Properties of Murine Perinatal and Adult Adipose Progenitor Subpopulations

Zhang et al. use single-cell transcriptomics to map the cellular landscape of perinatal murine epididymal adipose tissue, and demonstrate that altering the adipogenic capacity of perinatal adipose progenitors has long-term effects on progenitor plasticity, tissue expandability and metabolic health in adulthood. Adult white adipose tissue (WAT) harbors distinct mesenchymal stromal cell subpopulations that differentially affect WAT function and plasticity. Here we unveil the cellular landscape of the perinatal epididymal WAT primordium using single-cell transcriptomics in male mice. We reveal that adipocyte precursor cells and fibro-inflammatory progenitors (FIPs) emerge as functionally distinct PDGFR beta(+) subpopulations within the epididymal WAT anlagen prior to adipocyte accrual. We further identify important molecular and functional differences between perinatal and adult FIPs, including differences in their pro-inflammatory response, adipogenic capacity and anti-adipogenic behavior. Notably, we find that transient overexpression of Pparg in PDGFR beta(+) cells only during postnatal days 0.5 to 7.5 in male mice leads to hyperplastic WAT development, durable progenitor cell reprogramming, and protection against pathologic WAT remodeling and glucose intolerance in adult-onset obesity. Thus, factors that alter the adipogenic capacity of perinatal adipose progenitors can have long-lasting effects on progenitor plasticity, tissue expandability and metabolic health into adulthood.