Distinct Functional Properties of Perinatal Versus Adult Adipose Progenitor Subpopulations




Zhang, Qianbin

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The manner in which energy-storing white adipose tissue (WAT) expands and remodels in obesity is tightly linked to the development of metabolic syndrome. The recruitment of new fat cells ensures adequate energy storage in WAT and prevents against ectopic lipid accumulation and is therefore considered as "healthy expansion". Pathologic WAT expansion is characterized by chronic tissue inflammation and fibrosis, and is tightly linked to the development of diabetes. Our lab previously identified functionally distinct subpopulations of PDGFRβ+ perivascular progenitor cells within adult WAT depots that differentially impact tissue remodeling in obesity. PDGFRb+ APCs contribute to adipocyte hyperplasia associated with diet-induced obesity, whereas PDGFRb+ fibro-inflammatory progenitors, or "FIPs," regulate collagen deposition and inflammation in pathophysiological settings. My work aims to understand when and where these distinct cells emerge during the initial period of WAT development, and how manipulating the fate and function of these progenitors during the perinatal period can influence metabolism in adulthood. I used single-cell transcriptomics to unveil the cellular landscape of the perinatal murine epididymal WAT (eWAT) primordium. I reveal that adipocyte precursor cells (APCs) and fibro-inflammatory progenitors (FIPs) emerge as functionally distinct PDGFRb+ subpopulations within the eWAT anlagen prior to adipocyte accrual, at postnatal day 3 (P3). Importantly, I identify important molecular and functional differences between perinatal and adult FIPs, including differences in their pro-inflammatory response, adipogenic capacity, and anti-adipogenic behavior. Additionally, I found that transient overexpression of Pparg in PDGFRβ+ cells only during postnatal day 0.5 to 7.5 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.

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