Novel cell-to-cell communications between macrophages and fibroblasts regulate obesity-induced adipose tissue fibrosis [spatial transcriptomics]

Mincle (Macrophage inducible C-type lectin, clec4e) is a pattern recognition receptor expressed in innate immune cells and can sense cell death, suggesting a role in sterile inflammation. We previously showed that expression of Mincle is induced in adipose tissue macrophages during the development of obesity. Mincle accelerates adipose tissue inflammation and fibrosis, thereby exacerbating ectopic lipid accumulation and insulin resistance in the liver. In this study, we performed spatial transcriptomic analysis of the visceral adipose tissue from diet-induced obese mice to analyze distribution of Mincle-expressing macrophages and the gene expression around them. Male C57BL/6J mice were fed a standard diet or high-fat diet for 36 weeks. Spatial transcriptomic analysis was conducted using epididymal white adipose tissue.

Mincle（巨噬细胞诱导型C型凝集素，Macrophage inducible C-type lectin, CLEC4E）是一类表达于先天免疫细胞的模式识别受体（pattern recognition receptor），能够感知细胞死亡事件，提示其在无菌性炎症（sterile inflammation）中发挥关键调控作用。本团队此前研究发现，在肥胖发生过程中，脂肪组织巨噬细胞内Mincle的表达会被诱导上调。Mincle可促进脂肪组织炎症与纤维化进程，进而加剧肝脏内的异位脂质蓄积（ectopic lipid accumulation）与胰岛素抵抗（insulin resistance）。本研究针对饮食诱导肥胖小鼠（diet-induced obese mice）的内脏脂肪组织（visceral adipose tissue）开展空间转录组学分析（spatial transcriptomic analysis），以探究表达Mincle的巨噬细胞的分布特征及其周围的基因表达谱。实验中，雄性C57BL/6J小鼠被分别饲喂标准饲料与高脂饲料，持续36周。本次空间转录组学分析采用附睾白色脂肪组织（epididymal white adipose tissue）完成检测。