Single-cell sequencing of human white adipose tissue identifies new cell states in health and obesity.

Single-cell sequencing of human white adipose tissue identifies new cell states in health and obesity.
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DOI:
10.1038/s41590-021-00922-4
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发表时间:
2021-05
期刊:
影响因子:
30.5
通讯作者:
O'Sullivan TE
O'Sullivan TE
中科院分区:
医学1区
文献类型:
--
作者:
Hildreth AD;Ma F;Wong YY;Sun R;Pellegrini M;O'Sullivan TE

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白色脂肪组织(WAT)是能量储存和全身代谢稳态的重要调节因子。由免疫细胞和结构细胞组成的调节网络是维持WAT代谢所必需的,在哺乳动物肥胖期间,WAT代谢可能会受损。利用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WAT基质血管部分(SVF)的大规模全面细胞普查。我们报道了肥胖WAT中积累的脂肪固有淋巴样细胞(ILCs)、树突状细胞(dc)和单核细胞来源的巨噬细胞群的新亚群和发育轨迹。细胞-细胞配体受体相互作用和肥胖富集信号通路的分析揭示了从瘦WAT的免疫调节机制到肥胖WAT的炎症网络的转换。这些结果提供了健康人类WAT中稳态和炎症回路的详细和公正的细胞景观。
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 (SVF) of healthy lean and obese human WAT. We report novel subsets and developmental trajectories of adipose-resident innate lymphoid cells (ILCs), dendritic cells (DCs) 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.