ArticleMolecular cell2019
Landscape of Intercellular Crosstalk in Healthy and NASH Liver Revealed by Single-Cell Secretome Gene Analysis.
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Article in Molecular cell, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 524 papers.
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524 citing papers in PubMed, 749 citations in OpenAlex.
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464 more citing papers are in PubMed but not listed here.
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Authors and funding
30 authors at 7 institutions in 3 countries.
Xuelian XiongMinistry of Education Key Laboratory of Metabolism and Molecular Medicine, Department of Endocrinology and Metabolism, Zhongshan Hospital, Fudan University, Shanghai, China; Life Sciences Institute, University of Michigan, Ann Arbor, MI 48109, USA; Department of Cell & Developmental Biology, University of Michigan Medical Center, Ann Arbor, MI 48109, USA.
Henry KuangLife Sciences Institute, University of Michigan, Ann Arbor, MI 48109, USA; Department of Cell & Developmental Biology, University of Michigan Medical Center, Ann Arbor, MI 48109, USA.
Sahar AnsariDepartment of Human Genetics, University of Michigan Medical Center, Ann Arbor, MI 48109, USA.
Tongyu LiuLife Sciences Institute, University of Michigan, Ann Arbor, MI 48109, USA; Department of Cell & Developmental Biology, University of Michigan Medical Center, Ann Arbor, MI 48109, USA.
Jianke GongLife Sciences Institute, University of Michigan, Ann Arbor, MI 48109, USA; Department of Molecular and Integrative Physiology, University of Michigan Medical Center, Ann Arbor, MI 48109, USA; International Research Center for Sensory Biology and Technology of MOST, Key Laboratory of Molecular Biophysics of MOE, and College of Life Science and Technology, and Huazhong University of Science and Technology, Wuhan, Hubei, China.
Shuai WangDepartment of Biochemistry, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
Xu-Yun ZhaoLife Sciences Institute, University of Michigan, Ann Arbor, MI 48109, USA; Department of Cell & Developmental Biology, University of Michigan Medical Center, Ann Arbor, MI 48109, USA.
Yewei JiDepartment of Molecular and Integrative Physiology, University of Michigan Medical Center, Ann Arbor, MI 48109, USA.
Chuan LiDepartment of Immunology, School of Medicine, University of Connecticut, Farmington, CT 06030, USA.
Liang GuoLife Sciences Institute, University of Michigan, Ann Arbor, MI 48109, USA; Department of Cell & Developmental Biology, University of Michigan Medical Center, Ann Arbor, MI 48109, USA.
Linkang ZhouLife Sciences Institute, University of Michigan, Ann Arbor, MI 48109, USA; Department of Cell & Developmental Biology, University of Michigan Medical Center, Ann Arbor, MI 48109, USA.
Zhimin ChenLife Sciences Institute, University of Michigan, Ann Arbor, MI 48109, USA; Department of Cell & Developmental Biology, University of Michigan Medical Center, Ann Arbor, MI 48109, USA.
Paola Leon-MimilaDepartment of Medicine, Division of Cardiology, David Geffen School of Medicine, Los Angeles, CA, USA.
Meng Ting ChungDepartment of Mechanical Engineering, University of Michigan, Ann Arbor, MI 48105, USA.
Katsuo KurabayashiDepartment of Mechanical Engineering, University of Michigan, Ann Arbor, MI 48105, USA.
Judy OppUniversity of Michigan DNA Sequencing Core, University of Michigan, Ann Arbor, MI 48109, USA.
Francisco Campos-PérezClínica Integral de Cirugía para la Obesidad y Enfermedades Metabólicas, Hospital General Dr. Rubén Lénero, Mexico City, Mexico.
Hugo Villamil-RamírezFacultad de Química, UNAM/Instituto Nacional de Medicina Genómica (INMEGEN), Unidad de Genómica de Poblaciones Aplicada a la Salud, Mexico City, Mexico.
Samuel Canizales-QuinterosFacultad de Química, UNAM/Instituto Nacional de Medicina Genómica (INMEGEN), Unidad de Genómica de Poblaciones Aplicada a la Salud, Mexico City, Mexico.
Robert LyonsUniversity of Michigan DNA Sequencing Core, University of Michigan, Ann Arbor, MI 48109, USA.
Carey N LumengDepartment of Pediatrics and Communicable Diseases, University of Michigan Medical Center, Ann Arbor, MI 48109, USA.
Beiyan ZhouDepartment of Immunology, School of Medicine, University of Connecticut, Farmington, CT 06030, USA.
Ling QiDepartment of Molecular and Integrative Physiology, University of Michigan Medical Center, Ann Arbor, MI 48109, USA.
Adriana Huertas-VazquezDepartment of Medicine, Division of Cardiology, David Geffen School of Medicine, Los Angeles, CA, USA.
Aldons J LusisDepartment of Medicine, Division of Cardiology, David Geffen School of Medicine, Los Angeles, CA, USA.
X Z Shawn XuLife Sciences Institute, University of Michigan, Ann Arbor, MI 48109, USA; Department of Molecular and Integrative Physiology, University of Michigan Medical Center, Ann Arbor, MI 48109, USA.
Siming LiLife Sciences Institute, University of Michigan, Ann Arbor, MI 48109, USA; Department of Cell & Developmental Biology, University of Michigan Medical Center, Ann Arbor, MI 48109, USA.
Yonghao YuDepartment of Biochemistry, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
Jun Z LiDepartment of Human Genetics, University of Michigan Medical Center, Ann Arbor, MI 48109, USA.
Jiandie D LinLife Sciences Institute, University of Michigan, Ann Arbor, MI 48109, USA; Department of Cell & Developmental Biology, University of Michigan Medical Center, Ann Arbor, MI 48109, USA. Electronic address: jdlin@umich.edu.
University of Michigan · USUniversity of California, Los Angeles · USNational Institute of Genomic Medicine · MXThe University of Texas Southwestern Medical Center · USUniversity of Connecticut · USHospital General de México · MXSun Yat-sen University · CN
Funding
UCLA Clinical Translational Science InstituteUL1TR001881 · NCATS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI ARLEEN F. BROWN, ARASH NAEIM · 2016 to 2026
$118.1MMICHIGAN MEDICAL SCIENTIST TRAINING PROGRAMT32GM007863 · NIGMS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI COLLINS, KATHLEEN L. · 1985 to 2024
$38.3MPUBLIC HEALTH DEMONSTRATIONP60DK020572 · NIDDK · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI MYERS, MARTIN G · 1985 to 2012
$26.5MRegional Pilot And Feasibility Study Grants ProgramP30DK020572 · NIDDK · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Scott Soleimanpour · 2013 to 2026
$24.3MUniversity of Michigan Center for Gastrointestinal ResearchP30DK034933 · NIDDK · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI OWYANG, CHUNG · 1986 to 2021
$22.5MCELLULAR AND MOLECULAR BIOLOGY AT MICHIGANT32GM007315 · NIGMS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI PUTHENVEEDU, MANOJKUMAR A · 1985 to 2021
$12.8MMetabolic crosstalk through brown fat-enriched secreted factorsR01DK102456 · NIDDK · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Jiandie D Lin · 2015 to 2026
$4.9MNeural and genetic mechanisms underlying behavior in C. elegans - Administrative Supplement for Equipment PurchasesR35GM126917 · NIGMS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI XU, SHAWN · 2018 to 2025
$3.3MGlucose sensing by skeletal myocytesR01DK112800 · NIDDK · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI LIN, JIANDIE D · 2017 to 2021
$1.9MMicroRNA Regulated Macrophage Polarization in Adipose Tissue InflammationR01DK098662 · NIDDK · UNIVERSITY OF CONNECTICUT SCH OF MED/DNT · PI ZHOU, BEIYAN · 2013 to 2017
$1.6MMolecular and Biochemical Basis of mTORC1-mediated Feedback LoopsR01GM114160 · NIGMS · UT SOUTHWESTERN MEDICAL CENTER · PI YU, YONGHAO · 2015 to 2019
$1.6MHepatokine Regulation of Thermogenesis and Metabolic PhysiologyR01DK118731 · NIDDK · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI LIN, JIANDIE D · 2019 to 2022
$1.6MNCATS NIH HHS UL1 TR001881NIDDK NIH HHS F30 DK117615NIDDK NIH HHS P30 DK020572NIDDK NIH HHS P30 DK034933NIDDK NIH HHS P60 DK020572NIDDK NIH HHS R01 DK098662NIDDK NIH HHS R01 DK102456NIDDK NIH HHS R01 DK112800NIDDK NIH HHS R01 DK118731NIGMS NIH HHS R01 GM114160NIGMS NIH HHS R01 GM122932NIGMS NIH HHS R35 GM126917NIGMS NIH HHS T32 GM007315NIGMS NIH HHS T32 GM007863
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.
Indexed as
Sequence Analysis, RNAAnimalsCell CommunicationCellular ReprogrammingDisease Models, AnimalHepatic Stellate CellsHumansLigandsLiverMacrophagesMiceNon-alcoholic Fatty Liver DiseaseSignal TransductionSingle-Cell AnalysisLigandsHSCKupfferlivermacrophageNAFLDNASHNPCscRNA-seqsecretomesingle-cellstellakineTrem2
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