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.

Center for Infectious Medicine Department of Medicine Huddinge Karolinska Institutet Karolinska University Hospital Huddinge SE 141 52 Huddinge Sweden

Childhood Cancer Research Unit Department of Women's and Children's Health Karolinska Institutet SE 171 77 Stockholm Sweden

Department of Clinical Science Intervention and Technology Unit of Renal Medicine Karolinska Institutet Karolinska University Hospital Huddinge SE 141 86 Huddinge Sweden

Department of Human Biology NUTRIM School of Nutrition and Translational Research in Metabolism Maastricht University Medical Centre Maastricht the Netherlands

Department of Medicine Huddinge Karolinska Institutet Karolinska University Hospital Huddinge SE 141 83 Huddinge Sweden

Department of Metabolic Health Nestle Institute of Health Sciences Nestle Research Lausanne Switzerland

Department of Obesity and Nutritional Sciences The Novo Nordisk Foundation Hellerup Denmark

Franco Czech Laboratory for Clinical Research on Obesity 3rd Faculty of Medicine Charles University Prague and Université Toulouse 3 Paul Sabatier Toulouse France

Helmholtz Institute for Metabolic Obesity and Vascular Research of the Helmholtz Zentrum München at the University of Leipzig and University Hospital Leipzig Leipzig Germany

Institut Universitaire de France Paris France

Institute of Metabolic and Cardiovascular Diseases Université de Toulouse UMR1297 Toulouse France

Laboratoire de biochimie Centre Hospitalier Universitaire de Toulouse Toulouse France

Laboratory of Translational Nutrition Biology Institute of Food Nutrition and Health Department of Health Sciences and Technology ETH Zurich Schwerzenbach Switzerland

Medical Department 3 Endocrinology Nephrology Rheumatology University of Leipzig Medical Center Leipzig Germany

Science for Life Laboratory Department of Gene Technology KTH Royal Institute of Technology SE 171 65 Solna Sweden

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