A single cell 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. 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. Human samples: at BIDMC, potential subjects were recruited in a consecutive fashion, as scheduling permitted, from the gynecological, vascular, and general surgery rosters. Male and female subjects over the age of 18 undergoing elective plastic surgery procedures and free of other acute medical conditions were included and 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. The exclusion criteria were 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. At UPMC, inclusion criteria were patients receiving bariatric surgery or lean controls ages 21-60, exclusion criteria were diagnosis of diabetes (type 1 or type 2), pregnancy, alcohol or drug addiction, bleeding or clotting abnormality, or inflammatory abdominal disease. All patients 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. Mouse samples: Male and female C57Bl/6J 16-week old high fat diet fed (JAX 380050) and chow fed (JAX 380056) mice were obtained from The Jackson Laboratory and maintained on 60% high fat diet (Research Diets, D12492) or chow diet (8664 Harlan Teklad, 6.4% wt/wt fat), respectively, for three weeks before sacrifice. Mice were maintained under a 12 hr light/12hr dark cycle at constant temperature (23ºC) with free access to food and water. >>> Submitter declares that the human samples' raw data will be deposited in dbGaP due to patient privacy concerns. <<<白色脂肪组织（White adipose tissue, WAT）曾被认为在形态与功能上均乏善可陈，如今则被证实具有动态性、可塑性与异质性，并参与包括能量稳态、糖脂代谢调控、血压控制以及宿主防御在内的众多生物学过程。高脂喂养与其他代谢应激因子可导致脂肪组织的形态、生理特性与细胞组成发生显著改变，而脂肪量的变化与胰岛素抵抗、血脂异常及2型糖尿病（Type 2 diabetes, T2D）密切相关。 本研究提供了人类与啮齿类动物皮下及内脏白色脂肪组织在不同体重范围内的单细胞分辨率精细细胞图谱。我们鉴定出脂肪细胞、脂肪干细胞与祖细胞（adipose stem and progenitor cells, ASPCs）、血管细胞以及免疫细胞的亚群，并阐明了跨物种与膳食条件下的共性与差异。我们将特定细胞类型与代谢性疾病风险升高建立关联，并为瘦型与肥胖状态下脂肪微环境中各单个细胞类型间的全面相互作用提供了初步框架。本数据集为跨物种、脂肪沉积部位与营养条件下的白色脂肪组织功能相关基因、性状与细胞类型的研究提供了丰富的资源。 人类样本：在贝斯以色列女执事医疗中心（BIDMC），研究人员按照排班情况，从妇科、血管外科与普外科的接诊名单中连续招募符合条件的受试者。纳入标准为18岁以上、接受择期整形外科手术且无其他急性疾病的男女受试者，所有受试者术前均签署书面知情同意书。手术过程中经外科医生酌情采集手术部位的多余脂肪组织。排除标准包括服用噻唑烷二酮类药物、丙戊酸等染色质修饰酶调节剂、抗逆转录病毒药物，以及已知可诱导胰岛素抵抗的药物（如mTOR抑制剂或全身性糖皮质激素药物）的受试者。 在匹兹堡大学医学中心（UPMC），纳入标准为21-60岁接受减重代谢手术的患者及瘦型对照组受试者，排除标准包括确诊糖尿病（1型或2型）、妊娠、酒精或药物成瘾、出血或凝血异常、炎症性腹部疾病的患者。所有患者术前均签署书面知情同意书。手术过程中经外科医生酌情采集手术部位的多余脂肪组织。采集后立即将200-500mg的样本进行快速冷冻，用于后续下游实验处理。 小鼠样本：选用16周龄的雌雄C57BL/6J小鼠，高脂饲料喂养组（JAX 380050）与普通饲料喂养组（JAX 380056）均购自杰克逊实验室（The Jackson Laboratory）。两组小鼠分别在60%高脂饲料（Research Diets D12492）与普通饲料（Harlan Teklad 8664，脂肪含量为6.4%重量/重量）中饲养3周后实施安乐死。小鼠饲养环境为12小时光照/12小时黑暗循环，恒定温度23℃，自由进食饮水。 >>> 提交者声明，由于患者隐私问题，人类样本的原始数据将提交至dbGaP数据库。 <<<