| Literature DB >> 31398325 |
Xuelian Xiong1, Henry Kuang2, Sahar Ansari3, Tongyu Liu2, Jianke Gong4, Shuai Wang5, Xu-Yun Zhao2, Yewei Ji6, Chuan Li7, Liang Guo2, Linkang Zhou2, Zhimin Chen2, Paola Leon-Mimila8, Meng Ting Chung9, Katsuo Kurabayashi9, Judy Opp10, Francisco Campos-Pérez11, Hugo Villamil-Ramírez12, Samuel Canizales-Quinteros12, Robert Lyons10, Carey N Lumeng13, Beiyan Zhou7, Ling Qi6, Adriana Huertas-Vazquez8, Aldons J Lusis8, X Z Shawn Xu14, Siming Li2, Yonghao Yu5, Jun Z Li3, Jiandie D Lin15.
Abstract
Cell-cell communication via ligand-receptor signaling is a fundamental feature of complex organs. Despite this, the global landscape of intercellular signaling in mammalian liver has not been elucidated. Here we perform single-cell RNA sequencing on non-parenchymal cells isolated from healthy and NASH mouse livers. Secretome gene analysis revealed a highly connected network of intrahepatic signaling and disruption of vascular signaling in NASH. We uncovered the emergence of NASH-associated macrophages (NAMs), which are marked by high expression of triggering receptors expressed on myeloid cells 2 (Trem2), as a feature of mouse and human NASH that is linked to disease severity and highly responsive to pharmacological and dietary interventions. Finally, hepatic stellate cells (HSCs) serve as a hub of intrahepatic signaling via HSC-derived stellakines and their responsiveness to vasoactive hormones. These results provide unprecedented insights into the landscape of intercellular crosstalk and reprogramming of liver cells in health and disease.Entities:
Keywords: HSC; Kupffer; NAFLD; NASH; NPC; Trem2; liver; macrophage; scRNA-seq; secretome; single-cell; stellakine
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Year: 2019 PMID： 31398325 PMCID： PMC7262680 DOI： 10.1016/j.molcel.2019.07.028
Source DB: PubMed Journal: Mol Cell ISSN： 1097-2765 Impact factor: 17.970