Department of Microbiology, Immunology, and Molecular Genetics, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.
Molecular Biology Institute, University of California, Los Angeles, Los Angeles, CA, USA.
Nat Immunol. 2021 May;22(5):639-653. doi: 10.1038/s41590-021-00922-4. Epub 2021 Apr 27.
White adipose tissue (WAT) is an essential regulator of energy storage and systemic metabolic homeostasis. Regulatory networks consisting of immune and structural cells are necessary to maintain WAT metabolism, which can become impaired during obesity in mammals. Using single-cell transcriptomics and flow cytometry, we unveil a large-scale comprehensive cellular census of the stromal vascular fraction of healthy lean and obese human WAT. We report new subsets and developmental trajectories of adipose-resident innate lymphoid cells, dendritic cells and monocyte-derived macrophage populations that accumulate in obese WAT. Analysis of cell-cell ligand-receptor interactions and obesity-enriched signaling pathways revealed a switch from immunoregulatory mechanisms in lean WAT to inflammatory networks in obese WAT. These results provide a detailed and unbiased cellular landscape of homeostatic and inflammatory circuits in healthy human WAT.
白色脂肪组织(WAT)是能量储存和全身代谢稳态的重要调节剂。由免疫细胞和结构细胞组成的调节网络对于维持 WAT 代谢是必需的,而在哺乳动物肥胖时,WAT 代谢可能会受损。通过单细胞转录组学和流式细胞术,我们揭示了健康瘦人和肥胖人群 WAT 的基质血管部分的大规模全面细胞普查。我们报告了新的脂肪组织固有淋巴细胞、树突状细胞和单核细胞衍生巨噬细胞亚群的发育轨迹,这些细胞在肥胖的 WAT 中积累。对细胞-细胞配体-受体相互作用和肥胖富集信号通路的分析表明,从瘦 WAT 中的免疫调节机制转变为肥胖 WAT 中的炎症网络。这些结果为健康人 WAT 中的稳态和炎症回路提供了详细和无偏倚的细胞图谱。