Obesity-instructed TREM2-high macrophages identified by comparative analysis of diabetic mouse and human kidney at single-cell resolution [scRNA-seq: Baseline_mouse]

The cross-species molecular heterogeneity from mice to patients poses grand challenges for translational research endeavors. A high-fat diet (HFD) model and a genetic model (BTBR ob/ob) at different stand points were used to generate cell atlases of diabetic and obese mise. We identified a previously unrecognized, expanding Trem2-High macrophage population in kidneys of HFD mice that modeled human TREM2-high macrophages in obese patients. Taken together, our cross-species comparison highlights shared immune and metabolic cell-state changes. For establishing the baseline atlas, the most commonly used lab mouse strain C57BL/6J between ages of 10 and 12 weeks, was used. We included biological replicates (n=5 for coronal section, n= 3 for renal hilum, medulla, cortex) from both male (M) and female (F) sexes. A mouse either donated a coronal section or a section each of cortex, medulla and hilum.从小鼠到人类患者的跨物种分子异质性，为转化研究工作带来了重大挑战。本研究采用不同造模策略的高脂饮食（HFD）模型与遗传模型（BTBR ob/ob），构建了糖尿病与肥胖小鼠的细胞图谱。我们在高脂饮食小鼠的肾脏组织中，鉴定出一类此前未被报道的、呈扩增状态的高表达Trem2（Trem2）巨噬细胞群，该细胞群可模拟肥胖患者体内的高表达Trem2巨噬细胞表型。综上，本研究的跨物种比较分析揭示了保守存在的免疫与代谢细胞状态变化。为构建基线细胞图谱，本研究选用了当前最常用的实验小鼠品系C57BL/6J，其周龄为10至12周。本研究纳入了雄性（M）与雌性（F）小鼠的生物学重复样本：冠状脑切片样本量为n=5，肾门、肾髓质与肾皮质样本量均为n=3。每只小鼠仅提供冠状脑切片，或仅提供肾皮质、肾髓质与肾门各一份切片。