Generation of a Cellular Atlas of Human Adipose Tissue

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 defense.  High fat feeding and other metabolic stressors cause dramatic changes in adipose morphology, physiology, and cellular composition, and alterations in adiposity are associated with insulin resistance, dyslipidemia, and Type 2 diabetes (T2D). 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. We also utilize bulk RNA sequencing data of enzymatically digested human adipocytes to scale these findings to a larger cohort. 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.  ]]>
Number of subjects and manner of ascertainment:Whole cell Drop-seq: 9 subjectsSingle nucleus RNA sequencing: 13 subjectsBulk RNA sequencing and genotype profiling of floated adipocytes: 43 subjectsBeth Israel Deaconess Medical Center (BIDMC)Inclusion criteria: Male and female subjects over the age of 18 undergoing intra-abdominal or plastic surgery Exclusion criteria: Any subjects taking thiazolidinediones, chromatin-modifying enzymes such as valproic acid, anti-retroviral medications, and drugs known to induce insulin resistance such as mTOR inhibitors or systemic steroid medications All subjects were provided written informed consent preoperatively. Excess adipose tissue from the surgical site was collected at the discretion of the surgeon during the normal course of the procedure. University of Pittsburgh Medical Center (UPMC) Inclusion criteria: Patients receiving bariatric surgery or lean controls ages 21-60Exclusion criteria: Diagnosis of diabetes (type 1 or type 2)PregnancyAlcohol or drug addictionBleeding or clotting abnormalityInflammatory abdominal disease All subjects were provided written informed consent preoperatively. Excess adipose tissue from the surgical site was collected at the discretion of the surgeon during the normal course of the procedure. 200-500 mg samples were flash frozen immediately after collection for downstream processing.]]>