Single-nucleus transcriptome analysis identifies a novel FKBP5+ endothelial cell subtype involved in endothelial-to-mesenchymal transition in adipose tissue during aging

Age-associated adipose tissue (AT) dysfunction is multifactorial and often leads to detrimental health consequences. AT is highly vascularized and endothelial cells (ECs) has been recently identified as a key regulator in the homeostasis of AT. However, the alteration of cell composition in AT during aging and the communication between endothelial cells and adipocytes remain poorly understood. In this study, we take advantage of single nucleus RNA sequencing analysis, and discovered a group of FKBP5+ ECs specifically resident in aged AT. Of interest, FKBP5+ ECs exhibited the potential for endothelial-to-mesenchymal transition (EndoMT) and exhibited a critical role in regulating adipocytes. Furthermore, lineage tracing experiments demonstrated that ECs in aged AT tend to express FKBP5 and undergo EndoMT with progressive loss of endothelial marker. This study may provide a basis for a new mechanism of microvascular ECs-induced AT dysfunction during aging. •Distribution and functions of ECs' changes in adipose tissue during aging.•A novel subtype of FKBP5+ ECs can transform to a mesenchymal phenotype.•FKBP5+ECs increase during aging in mice AT and behave more mesenchymal features.•Identified cell-cell communications between FKBP5+ ECs and adipocyte.