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. 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.

单细胞测序技术（Single Cell Sequencing）正为学界带来超出预期的深刻洞见：原本看似均质的细胞群体，其功能特性往往存在显著差异；而多样化的细胞组成谱可介导组织与器官的生理功能。脂肪组织（Adipose Tissue）可调控系统性能量稳态（Systemic Energy Homeostasis）的多个关键环节，但截至目前仅报道过两种人类脂肪细胞亚型（Adipocyte Subtype）。本研究开发了人类单个间充质祖细胞（Mesenchymal Progenitors）的表征技术，并借此发现了四种此前未被报道的脂肪细胞亚型：这些亚型分别适配不同的脂肪组织生理功能，且各自起源于特异的祖细胞群体。明确这类不同脂肪细胞亚型及其祖细胞的存在，将有助于我们阐明调控其丰度与特性的分子机制，进而更深入地理解这些机制失调如何引发代谢性疾病（Metabolic Disease）。本分析共纳入52株源自人类皮下脂肪组织（Subcutaneous Adipose Tissue）的祖细胞，这些细胞分别在3种处理条件下培养：对照组（Control，简称C）、MDI组（简称M）及福司柯林（Forskolin，简称F）处理组。