Single-cell RNA sequencing reveals a novel inhibitory effect of ApoA4 on NAFL mediated by liver-specific subsets of myeloid cells

• DOI: 10.3389/fimmu.2022.1038401
• Publication Date: 2022-11-08T04:47:26Z
• Authors: Xiao-Huan Liu; Jin-Ting Zhou; Chun-xia Yan; Cheng Cheng; Jing-Na Fan; Jing Xu; Qiangsun Zheng; Qiang Bai; Zongfang Li; Shengbin Li; Xiaoming Li
• Keywords: CXCL2

The liver immune microenvironment is a key element in the development of hepatic inflammation NAFLD. ApoA4 deficiency increases lipid burden, insulin resistance, and metabolic inflammation. However, effect on cells precise cell subsets that exacerbate fatty remain elusive. aim this study was to profile affected by NAFL. We performed scRNA-seq from WT ApoA4-deficient mice administered high-fat diet. Immunostaining qRT-PCR analysis were used validate results scRNA-seq. identified 10 discrete populations comprising macrophages, DCs, granulocytes, B, T NK&NKT characterized their subsets, gene expression profiles, functional modules. led significant abundance specific including inflammatory macrophages (2-Mφ-Cxcl9 4-Mφ-Cxcl2) activated granulocytes (0-Gran-Wfdc17). Moreover, resulted higher Lgals3, Ctss, Fcgr2b, Spp1, Cxcl2, Elane levels lower Nr4a1 cells. These genes consistent with human NAFLD-associated marker linked disease severity. NE IL-1β as targets presence or absence immunostaining. data analyses revealed reprogramming deficiency. uncovered emergence ApoA4-associated (namely Cxcl9+ macrophage, Cxcl2+ macrophage Wfdc17+ granulocyte), pathways, NAFLD-related may promote findings provide novel therapeutic for NAFL foundations further studying effects various diseases.