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.

The composition,function,and regulation of adipose stem and progenitor cells

White adipose tissue(WAT)is a highly plastic organ that plays a central role in regulating whole-body energy metabolism.Adipose stem and progenitor cells(ASPCs)are essential components of the stromal vascular fraction(SVF)of adipose tissue.They give rise to mature adipocytes and play a critical role in maintaining adipose tissue function.However,the molecular heterogeneity and functional diversity of ASPCs are still poorly understood.Recently,single-cell RNA sequencing(scRNA-seq)analysis has identified distinct subtypes of ASPCs in murine and human adipose tissues,providing new insights into the cellular complexity of ASPCs among multiple fat depots.This review summarizes the current knowledge on ASPC populations,including their markers,functions,and regulatory mechanisms.Targeting one or several of these cell populations may ameliorate metabolic disorders by promoting adaptive hyperplastic adipose growth.