Single-nucleus RNA sequencing reveals heterogeneity among multiple white adipose tissue depots

Regardless of its anatomical site,adipose tissue shares a common energy-storage role but exhibits distinctive properties.Exploring the cellular and molecular heterogeneity of white adipose tissue(WAT)is crucial for comprehending its function and properties.However,existing single-nucleus RNA sequencing(snRNA-seq)studies of adipose tissue heterogeneity have examined only one or two depots.In this study,we employed snRNA-seq to test five representative depots including inguinal,epididymal,mesenteric,perirenal,and pericardial adipose tissues in mice under physiological conditions.By analyzing the contents of main cell catego-ries and gene profiles of various depots,we identified their distinctive physiological properties.Immune cells and fibro-adipogenic progenitor cells(FAPs)showed dramatic differences among WAT depots,while adipocytes seemed to be conserved.The heightened presence of regulatory macrophages and B cells in pericardial adipose tissues implied their potential contribution to the preservation of coronary vascular function.Moreover,the selective aggregation of pericytes within mesenteric adipose tissue was likely associated with the maintenance of intestinal barrier homeostasis.Using a combination of RNA sequencing and snRNA-seq analysis,the major subpopulations of FAPs derived from these depots determined the site characteristics of FAPs to a certain extent.Our work estab-lishes a systematic and reliable foundation for investigating the heterogeneity of WAT depots and elucidating the unique roles these depots play in coordinating the function of adjacent organs.

Cold-Induced Reprogramming of Subcutaneous White Adipose Tissue Assessed by Single-Cell and Single-Nucleus RNA Sequencing

Adipose browning has demonstrated therapeutic potentials in several diseases.Here,by conducting transcriptomic profiling at the single-cell and single-nucleus resolution,we reconstituted the cellular atlas in mouse inguinal subcutaneous white adipose tissue(iWAT)at thermoneutrality or chronic cold condition.All major nonimmune cells within the iWAT,including adipose stem and progenitor cells(ASPCs),mature adipocytes,endothelial cells,Schwann cells,and smooth muscle cells,were recovered,allowing us to uncover an overall and detailed blueprint for transcriptomes and intercellular cross-talks and the dynamics during white adipose tissue brown remodeling.Our findings also unravel the existence of subpopulations in mature adipocytes,ASPCs,and endothelial cells,as well as new insights on their interconversion and reprogramming in response to cold.The adipocyte subpopulation competent of major histocompatibility complex class Ⅱ(MHCⅡ)antigen presentation is potentiated.Furthermore,a subcluster of ASPC with CD74 expression was identified as the precursor of this MHCⅡ^(+)adipocyte.Beige adipocytes are transdifferented from preexisting lipid generating adipocytes,which exhibit developmental trajectory from de novo differentiation of amphiregulin cells(Aregs).Two distinct immune-like endothelial subpopulations are present in iWAT and are responsive to cold.Our data reveal fundamental changes during cold-evoked adipose browning.