Expansion of macrophage and liver sinusoidal endothelial cell subpopulations during non-alcoholic steatohepatitis progression
Zhenyang Shen, Bo Shen, Weiming Dai, Cui Zhou, Xin Luo, Yuecheng Guo, Junjun Wang, Xianjun Xu, Zhongshang Sun, Xiaobo Cai, Hui Dong, Lungen Lu
Abstract
Liver non-parenchymal cells (NPCs) play a critical role in the progression of non-alcoholic steatohepatitis (NASH). We aimed to explore the heterogeneity of NPCs and identify NASH-specific subpopulations contributing to NASH progression. Through single-cell RNA sequencing, we uncovered a proinflammatory subpopulation of Itgad hi /Fcrl5 hi macrophages with potential function of modulating macrophage accumulation and promoting NASH development. We also identified subpopulations of Egr1 hi and Ly6a hi liver sinusoidal endothelial cells (LSECs), which might participate in pathological angiogenesis and inflammation regulation. The Itgad hi /Fcrl5 hi macrophages, Egr1 hi LSECs, and Ly6a hi LSECs emerged in the early stage and expanded significantly along with pathological progression of liver injury during NASH. Cell-cell interactions between hepatic stellate cells (HSCs) and Itgad hi /Fcrl5 hi macrophages, Egr1 hi LSECs or Ly6a hi LSECs were enhanced in NASH liver. Our results revealed that expansion of Itgad hi /Fcrl5 hi macrophages, Egr1 hi LSECs or Ly6a hi LSECs was strongly associated with NASH severity, suggesting these subpopulations might be involved in NASH progression.