The complex relationship between metabolic disease risk and body fat distribution in humans involves cellular characteristics which are specific to body fat compartments. Here we show depot-specific differences in the stromal vascual fraction of visceral and subcutaneous adipose tissue by performing single-cell RNA sequencing of tissue specimen from obese individuals. We characterize multiple immune cells, endothelial cells, fibroblasts, adipose and hematopoietic stem cell progenitors. Subpopulations of adipose-resident immune cells are metabolically active and associated with metabolic disease status and those include a population of potential dysfunctional CD8+ T cells expressing metallothioneins. We identify multiple types of adipocyte progenitors that are common across depots, including a subtype enriched in individuals with type 2 diabetes. Depot-specific analysis reveals a class of adipocyte progenitors unique to visceral adipose tissue, which shares common features with beige preadipocytes. Our human single-cell transcriptome atlas across fat depots provides a resource to dissect functional genomics of metabolic disease.
Conflict of interest statement
Declaration of Interests A.T. receives funding from Johnson & Johnson Medical Companies and Medtronic for research unrelated to the present manuscript.
Characterization of stromal vascular fraction and adipose stem cells from subcutaneous, preperitoneal and visceral morbidly obese human adipose tissue depots.PLoS One. 2017 Mar 21;12(3):e0174115. doi: 10.1371/journal.pone.0174115. eCollection 2017. PLoS One. 2017. PMID: 28323901 Free PMC article.
Identification of depot-specific human fat cell progenitors through distinct expression profiles and developmental gene patterns.Am J Physiol Endocrinol Metab. 2007 Jan;292(1):E298-307. doi: 10.1152/ajpendo.00202.2006. Epub 2006 Sep 19. Am J Physiol Endocrinol Metab. 2007. PMID: 16985259
Comparison of proliferation and differentiation capacity of human adipocyte precursor cells from the omental and subcutaneous adipose tissue depot of obese subjects.Metabolism. 2004 May;53(5):632-7. doi: 10.1016/j.metabol.2003.11.012. Metabolism. 2004. PMID: 15131769
Control of adipocyte differentiation in different fat depots; implications for pathophysiology or therapy.Front Endocrinol (Lausanne). 2015 Jan 30;6:1. doi: 10.3389/fendo.2015.00001. eCollection 2015. Front Endocrinol (Lausanne). 2015. PMID: 25688231 Free PMC article. Review.
The sexual dimorphism of obesity.Mol Cell Endocrinol. 2015 Feb 15;402:113-9. doi: 10.1016/j.mce.2014.11.029. Epub 2015 Jan 8. Mol Cell Endocrinol. 2015. PMID: 25578600 Free PMC article. Review.
Cited by 1 article
An Eclectic Cast of Cellular Actors Orchestrates Innate Immune Responses in the Mechanisms Driving Obesity and Metabolic Perturbation.Circ Res. 2020 May 22;126(11):1565-1589. doi: 10.1161/CIRCRESAHA.120.315900. Epub 2020 May 21. Circ Res. 2020. PMID: 32437306