Identification of metabolically distinct adipocyte progenitor cells in human adipose tissues

Adipocyte progenitor cells (APCs) provide the reservoir of regenerative cells to produce new adipocytes, although their identity in humans remains elusive. Using FACS analysis, gene expression profiling and metabolic and proteomic analyses, we identified three APCs subtypes in human white adipose tissues. The APC subtypes are molecularly distinct but possess similar proliferative and adipogenic capacities. Adipocytes derived from APCs with high CD34 expression exhibit exceedingly high rates of lipid flux compared with APCs with low or no CD34 expression, while adipocytes produced from CD34- APCs display beige-like adipocyte properties and a unique endocrine profile. APCs were more abundant in gluteofemoral compared with abdominal subcutaneous and omental adipose tissues, and the distribution of APC subtypes varies between depots and in patients with type 2 diabetes. These findings provide a mechanistic explanation for the heterogeneity of human white adipose tissue and a potential basis for dysregulated adipocyte function in type 2 diabetes. Overall design: Molecular, biochemical and clinical examination of three cell types wthin the stromal vascular fraction of human adipose tissue.

脂肪细胞祖细胞（Adipocyte progenitor cells, APCs）是生成新生脂肪细胞的再生细胞储备库，但其在人体内的身份特征仍不明确。本研究通过荧光激活细胞分选（Fluorescence-Activated Cell Sorting, FACS）分析、基因表达谱分析以及代谢组和蛋白质组学分析，在人类白色脂肪组织中鉴定出三种APCs亚型。这些APCs亚型在分子层面具有显著差异，但具备相似的增殖与成脂分化能力。分化簇34（CD34）高表达APCs分化得到的脂肪细胞，与CD34低表达或不表达的APCs来源的脂肪细胞相比，具有极高的脂质流动速率；而CD34阴性（CD34-）APCs分化产生的脂肪细胞则呈现米色样脂肪细胞特性，以及独特的内分泌特征谱。APCs在臀股部脂肪组织中的丰度高于腹部皮下脂肪组织和网膜脂肪组织，且APCs亚型的分布在不同脂肪沉积部位以及2型糖尿病患者体内存在差异。上述研究结果为人类白色脂肪组织的异质性提供了机制层面的解释，也为2型糖尿病患者脂肪细胞功能失调提供了潜在的理论基础。研究整体设计：对人类脂肪组织基质血管组分（Stromal Vascular Fraction, SVF）内的三种细胞类型开展分子、生化与临床检测。