Diverse repertoire of human adipocyte subtypes develops from transcriptionally distinct mesenchymal progenitor cells

Single cell sequencing technologies are providing unexpected insights on how seemingly homogenous cell populations differ markedly in their functional properties, and how diverse cell repertoires mediate the functions of tissues and organs. Adipose tissue controls multiple key aspects of systemic energy homeostasis, but only two human adipocyte subtypes have been recognized so far. Here we developed methods to characterize single human mesenchymal progenitors and discovered four previously unknown adipocyte subtypes specialized for distinct adipose tissue functions, which are derived from distinct progenitors. Recognizing the existence of these different adipocyte subtypes and their progenitors will allow us to elucidate mechanisms that control their abundance and properties, and to better understand how dysregulation of these mechanisms can lead to metabolic disease. Overall design: Human subcutaneous adipose tissue derived progenitor cells 52 clones under 3 treatment conditions (Control (C), MDI (M) and Forskolin (F)) are included in the analysis.