These studies suggest that separate cell types provide thermogenesis, insulin sensitivity, lipid storage and adipokine secretion 9, 10, 11 or act as negative regulators of lipid accumulation 12. Single-cell technologies have allowed an understanding of the heterogeneity of adipocytes, revealing several subtypes with specialized functions 6, 7, 8. Intriguingly, progenitor cells derived from the seasonally plastic white adipose tissue (WAT) of brown bears spontaneously differentiated into osteocytes in vitro 5, further emphasizing the developmental link between these two cell types. Other studies have shown a close relation between osteocytes and adipocytes, with opposing differentiation trajectories mediated through a common transcriptional network 4. Adipocytes originate from mesenchymal stem cells that reside in multiple tissues including adipose tissue, skeletal muscle and bone marrow 3. Brown adipose tissue (BAT) activity is also associated with metabolic health 2. Multiple studies have described that abdominal obesity is strongly associated with cardiovascular disease and insulin resistance, whereas accumulation of fat in the lower gynoid regions has a lower lipid turnover and is associated with metabolic health 1. In conclusion, we provide a differentiation map of human adipocytes and define the multipotent SWAT cell, providing a new perspective on adipose tissue regulation.īody fat distribution and adipocyte functionality are determinants of metabolic health in a depot-dependent fashion. Label transfer algorithms recapitulate the cell types in human adipose tissue datasets. When stripped from adipogenic cells, SWAT cells display a multipotent phenotype by reverting towards progenitor state or differentiating into new adipogenic cells, dependent on media. Based on an extracellular matrix and developmental gene signature, we name the structural branch of cells structural Wnt-regulated adipose tissue-resident (SWAT) cells. The adipogenic gene signature contains mitochondrial activity genes, and associates with genome-wide association study traits for fat distribution. We show at single-cell resolution that progenitor cells from four human brown and white adipose depots separate into two main cell fates, an adipogenic and a structural branch, developing from a common progenitor. Adipocyte function is a major determinant of metabolic disease, warranting investigations of regulating mechanisms.
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