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Abstract
To date, single-cell studies of human white adipose tissue (WAT) have been based on small cohort sizes and no cellular consensus nomenclature exists. Herein, we performed a comprehensive meta-analysis of publicly available and newly generated single-cell, single-nucleus, and spatial transcriptomic results from human subcutaneous, omental, and perivascular WAT. Our high-resolution map is built on data from ten studies and allowed us to robustly identify >60 subpopulations of adipocytes, fibroblast and adipogenic progenitors, vascular, and immune cells. Using these results, we deconvolved spatial and bulk transcriptomic data from nine additional cohorts to provide spatial and clinical dimensions to the map. This identified cell-cell interactions as well as relationships between specific cell subtypes and insulin resistance, dyslipidemia, adipocyte volume, and lipolysis upon long-term weight changes. Altogether, our meta-map provides a rich resource defining the cellular and microarchitectural landscape of human WAT and describes the associations between specific cell types and metabolic states.
Single-cell studies of human white adipose tissue (WAT) provide insights into the specialized cell types in the tissue. Here the authors combine publicly available and newly generated high-resolution and bulk transcriptomic results from multiple human datasets to provide a comprehensive cellular map of white adipose tissue.
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1 Karolinska University Hospital Huddinge, Department of Medicine Huddinge (H7), Karolinska Institutet, Huddinge, Sweden (GRID:grid.24381.3c) (ISNI:0000 0000 9241 5705)
2 ETH Zurich, Laboratory of Translational Nutrition Biology, Institute of Food, Nutrition and Health, Department of Health Sciences and Technology, Schwerzenbach, Switzerland (GRID:grid.5801.c) (ISNI:0000 0001 2156 2780)
3 Obesity and Vascular Research (HI-MAG) of the Helmholtz Zentrum München at the University of Leipzig and University Hospital Leipzig, Helmholtz Institute for Metabolic, Leipzig, Germany (GRID:grid.411339.d) (ISNI:0000 0000 8517 9062)
4 Karolinska Institutet, Karolinska University Hospital Huddinge, Center for Infectious Medicine, Department of Medicine Huddinge (H7), Huddinge, Sweden (GRID:grid.4714.6) (ISNI:0000 0004 1937 0626)
5 Karolinska Institutet, Karolinska University Hospital Huddinge, Center for Infectious Medicine, Department of Medicine Huddinge (H7), Huddinge, Sweden (GRID:grid.4714.6) (ISNI:0000 0004 1937 0626); Karolinska Institutet, Childhood Cancer Research Unit, Department of Women’s and Children’s Health, Stockholm, Sweden (GRID:grid.4714.6) (ISNI:0000 0004 1937 0626)
6 Unit of Renal Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge, Department of Clinical Science, Intervention & Technology (CLINTEC), Huddinge, Sweden (GRID:grid.4714.6) (ISNI:0000 0004 1937 0626)
7 KTH Royal Institute of Technology, Science for Life Laboratory, Department of Gene Technology, Solna, Sweden (GRID:grid.5037.1) (ISNI:0000000121581746)
8 Nestle Institute of Health Sciences, Nestle Research, Department of Metabolic Health, Lausanne, Switzerland (GRID:grid.419905.0) (ISNI:0000 0001 0066 4948)
9 The Novo Nordisk Foundation, Department of Obesity and Nutritional Sciences, Hellerup, Denmark (GRID:grid.487026.f) (ISNI:0000 0000 9922 7627)
10 Maastricht University Medical Centre(+), Department of Human Biology, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht, the Netherlands (GRID:grid.412966.e) (ISNI:0000 0004 0480 1382)
11 Université Toulouse III - Paul Sabatier (UPS), Université de Toulouse, Institute of Metabolic and Cardiovascular Diseases (I2MC), Institut National de la Santé et de la Recherche Médicale (Inserm), Toulouse, France (GRID:grid.15781.3a) (ISNI:0000 0001 0723 035X); Charles University, Prague and Université Toulouse III - Paul Sabatier (UPS), Franco-Czech Laboratory for Clinical Research on Obesity, Third Faculty of Medicine, Toulouse, France (GRID:grid.15781.3a) (ISNI:0000 0001 0723 035X)
12 Université Toulouse III - Paul Sabatier (UPS), Université de Toulouse, Institute of Metabolic and Cardiovascular Diseases (I2MC), Institut National de la Santé et de la Recherche Médicale (Inserm), Toulouse, France (GRID:grid.15781.3a) (ISNI:0000 0001 0723 035X); Charles University, Prague and Université Toulouse III - Paul Sabatier (UPS), Franco-Czech Laboratory for Clinical Research on Obesity, Third Faculty of Medicine, Toulouse, France (GRID:grid.15781.3a) (ISNI:0000 0001 0723 035X); Centre Hospitalier Universitaire de Toulouse, Laboratoire de biochimie, Toulouse, France (GRID:grid.411175.7) (ISNI:0000 0001 1457 2980); Institut Universitaire de France (IUF), Paris, France (GRID:grid.440891.0) (ISNI:0000 0001 1931 4817)
13 Obesity and Vascular Research (HI-MAG) of the Helmholtz Zentrum München at the University of Leipzig and University Hospital Leipzig, Helmholtz Institute for Metabolic, Leipzig, Germany (GRID:grid.411339.d) (ISNI:0000 0000 8517 9062); University of Leipzig Medical Center, Medical Department III - Endocrinology, Nephrology, Rheumatology, Leipzig, Germany (GRID:grid.9647.c) (ISNI:0000 0004 7669 9786)