A single cell atlas of human and mouse white adipose tissue

Abstract

White adipose tissue (WAT), once regarded as morphologically and functionally bland, is now recognized to be dynamic, plastic, heterogenous, and involved in a wide array of biological processes including energy homeostasis, glucose and lipid handling, blood pressure control, and host defense1. High fat feeding and other metabolic stressors cause dramatic changes in adipose morphology, physiology, and cellular composition1, and alterations in adiposity are associated with insulin resistance, dyslipidemia, and type 2 diabetes (T2D)2. Here, we provide detailed cellular atlases of human and murine subcutaneous and visceral white fat at single cell resolution across a range of body weight. We identify subpopulations of adipocytes, adipose stem and progenitor cells (ASPCs), vascular, and immune cells and demonstrate commonalities and differences across species and dietary conditions. We link specific cell types to increased risk of metabolic disease, and we provide an initial blueprint for a comprehensive set of interactions between individual cell types in the adipose niche in leanness and obesity. These data comprise an extensive resource for the exploration of genes, traits, and cell types in the function of WAT across species, depots, and nutritional conditions.

Transcriptome and fatty-acid signatures of adipocyte hypertrophy and its non-invasive MR-based characterization in human adipose tissue

“…The stronger association between adipocyte area and predicted thermogenic adipocyte content in VAT compared to SAT is in good agreement with recent WAT single cell transcriptomics studies reporting the presence of beige-like adipocyte progenitors and thermogenic subpopulations predominantly in VAT. 31 , 55 …”

“…The described associations are in good agreement with a recent study that reports positive associations between predicted myeloid/lymphoid immune cell proportions and BMI. 31 Large parts of the stromal vascular fraction consist of immune cells and proportions are known to change with obesity contributing to a pro-inflammatory environment. Our data on T cells and adipocyte area relate well to studies reporting increased amounts, but also differing T cell subtypes with obesity.…”

“… 30 Marker genes for human cell-type clusters were derived from a recently published single cell atlas of human and mouse white adipose tissue. 31 Relative differences in cell-type abundances predicted by Bisque were correlated with GTEx adipocyte area estimates. Group-wise comparisons were used to assess differences in cell type proportions between isolated mature adipocyte fractions and preadipocytes.…”

A Neurogenic Signature Involving Monoamine Oxidase-A controls Human Thermogenic Adipose Tissue Development

“…The vasculature of the hybrid tissue may also be critical in defining its immune composition. We find that the relative proportion of immune cells in the hybrid tissue resembles that of mouse adipose tissue, which differs from human by having a relatively high macrophage content [48]. Cells within the vasculature, such as endothelial or progenitor cells, might be more important in defining the immune composition of adipose tissue than adipocytes [49, 50].…”

White Adipose Tissue Compositional and Transcriptional Patterns with Progressive Glucose Intolerance in Persons with HIV

“…Several studies have used single-cell RNA sequencing (scRNA-seq) to characterize the cellular composition in the adipose tissue compartment in mice and humans, primarily in the context of obesity research (Acosta et al, 2017; Emont et al, 2022; Hildreth et al, 2021; Merrick et al, 2019; Sarvari et al, 2021; Vijay et al, 2020). However, there are currently few data on the cellular composition of adipose tissue in the context of metabolic disease and diabetes, particularly among groups at elevated risk such as PWH.…”