Human subcutaneous and visceral adipocyte atlases uncover classical and non-classical adipocytes and depot-specific patterns
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ABSTRACT:
PROVIDER: PRJNA1183538 | ENA |
REPOSITORIES: ENA
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Project description:The complex relationship between metabolic disease risk and body fat distribution in humans involves cellular characteristics which are specific to each body fat compartment. We applied single-cell RNA sequencing (scRNA-Seq) to identify these depot-specific differences in the stromal vascular fraction of visceral (VAT) and subcutaneous (SAT) adipose tissue of obese individuals. We characterized multiple immune cells, endothelial cells, fibroblasts, adipose and hematopoietic stem cell progenitors. Subpopulations of adipose-resident immune cells were found to be metabolically active and associated with metabolic disease status including a population of potential dysfunctional CD8+ T cells expressing metallothioneins. Adipocyte progenitors were identified at different stages of adipogenesis where a subset was pronounced in type 2 diabetics. Depot-specific analysis revealed a class of adipocyte progenitors unique to VAT possessing features similar to ‘inducible brown preadipocytes’. Our first generation human scRNA-Seq transcriptome atlas across fat depots provides a new resource to dissect functional genomics of metabolic disease.
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Project description:In humans, adipose tissue is distributed in subcutaneous abdominal and subcutaneous gluteal depots that comprise a variety of functional differences. Whereas energy storage in gluteal adipose tissue has been shown to mediate a protective effect, an increase of abdominal adipose tissue is associated with metabolic disorders. However, the molecular basis of depot-specific characteristics is not completely understood yet. Using array-based analyses of transcription profiles, we identified a specific set of genes that was differentially expressed between subcutaneous abdominal and gluteal adipose tissue. To investigate the role of epigenetic regulation in depot-specific gene expression, we additionally analyzed genome-wide DNA methylation patterns in abdominal and gluteal depots. By combining both data sets, we identified a highly significant set of depot-specifically expressed genes that appear to be epigenetically regulated. Interestingly, the majority of these genes form part of the homeobox gene family. Moreover, genes involved in fatty acid metabolism were also differentially expressed. Therefore we suppose that changes in gene expression profiles might account for depot-specific differences in lipid composition. Indeed, triglycerides and fatty acids of abdominal adipose tissue were more saturated compared to triglycerides and fatty acids in gluteal adipose tissue. Taken together, our results uncover clear differences between abdominal and gluteal adipose tissue on the gene expression and DNA methylation level as well as in fatty acid composition. Therefore, a detailed molecular characterization of adipose tissue depots will be essential to develop new treatment strategies for metabolic syndrome associated complications.
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