Landscape of Intercellular Crosstalk in Healthy and NASH Liver Revealed by Single-Cell Secretome Gene Analysis

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 NA...

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Vydáno v:Molecular cell Ročník 75; číslo 3; s. 644
Hlavní autoři: Xiong, Xuelian, Kuang, Henry, Ansari, Sahar, Liu, Tongyu, Gong, Jianke, Wang, Shuai, Zhao, Xu-Yun, Ji, Yewei, Li, Chuan, Guo, Liang, Zhou, Linkang, Chen, Zhimin, Leon-Mimila, Paola, Chung, Meng Ting, Kurabayashi, Katsuo, Opp, Judy, Campos-Pérez, Francisco, Villamil-Ramírez, Hugo, Canizales-Quinteros, Samuel, Lyons, Robert, Lumeng, Carey N, Zhou, Beiyan, Qi, Ling, Huertas-Vazquez, Adriana, Lusis, Aldons J, Xu, X Z Shawn, Li, Siming, Yu, Yonghao, Li, Jun Z, Lin, Jiandie D
Médium: Journal Article
Jazyk:angličtina
Vydáno: United States 08.08.2019
Témata:
Animals
Cell Communication - genetics
Cellular Reprogramming - genetics
Disease Models, Animal
Hepatic Stellate Cells - metabolism
Hepatic Stellate Cells - pathology
Humans
Ligands
Liver - metabolism
Liver - pathology
Macrophages - metabolism
Macrophages - pathology
Mice
Non-alcoholic Fatty Liver Disease - genetics
Non-alcoholic Fatty Liver Disease - metabolism
Non-alcoholic Fatty Liver Disease - pathology
Sequence Analysis, RNA
Signal Transduction - genetics
Single-Cell Analysis
NPC
NAFLD
scRNA-seq
liver
Kupffer
single-cell
HSC
Trem2
macrophage
NASH
secretome
stellakine
ISSN:1097-4164, 1097-4164
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Shrnutí: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.
Bibliografie:ObjectType-Article-1
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ISSN:1097-4164
1097-4164
DOI:10.1016/j.molcel.2019.07.028