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Landscape of Intercellular Crosstalk in Healthy and NASH Liver Revealed by Single-Cell Secretome Gene Analysis.
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.
Afiliação
  • Xiong X; Ministry 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, Uni
  • Kuang H; 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.
  • Ansari S; Department of Human Genetics, University of Michigan Medical Center, Ann Arbor, MI 48109, USA.
  • Liu T; 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.
  • Gong J; Life 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 Biophy
  • Wang S; Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
  • Zhao XY; 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.
  • Ji Y; Department of Molecular and Integrative Physiology, University of Michigan Medical Center, Ann Arbor, MI 48109, USA.
  • Li C; Department of Immunology, School of Medicine, University of Connecticut, Farmington, CT 06030, USA.
  • Guo L; 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.
  • Zhou L; 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.
  • Chen Z; 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.
  • Leon-Mimila P; Department of Medicine, Division of Cardiology, David Geffen School of Medicine, Los Angeles, CA, USA.
  • Chung MT; Department of Mechanical Engineering, University of Michigan, Ann Arbor, MI 48105, USA.
  • Kurabayashi K; Department of Mechanical Engineering, University of Michigan, Ann Arbor, MI 48105, USA.
  • Opp J; University of Michigan DNA Sequencing Core, University of Michigan, Ann Arbor, MI 48109, USA.
  • Campos-Pérez F; Clínica Integral de Cirugía para la Obesidad y Enfermedades Metabólicas, Hospital General Dr. Rubén Lénero, Mexico City, Mexico.
  • Villamil-Ramírez H; Facultad de Química, UNAM/Instituto Nacional de Medicina Genómica (INMEGEN), Unidad de Genómica de Poblaciones Aplicada a la Salud, Mexico City, Mexico.
  • Canizales-Quinteros S; Facultad de Química, UNAM/Instituto Nacional de Medicina Genómica (INMEGEN), Unidad de Genómica de Poblaciones Aplicada a la Salud, Mexico City, Mexico.
  • Lyons R; University of Michigan DNA Sequencing Core, University of Michigan, Ann Arbor, MI 48109, USA.
  • Lumeng CN; Department of Pediatrics and Communicable Diseases, University of Michigan Medical Center, Ann Arbor, MI 48109, USA.
  • Zhou B; Department of Immunology, School of Medicine, University of Connecticut, Farmington, CT 06030, USA.
  • Qi L; Department of Molecular and Integrative Physiology, University of Michigan Medical Center, Ann Arbor, MI 48109, USA.
  • Huertas-Vazquez A; Department of Medicine, Division of Cardiology, David Geffen School of Medicine, Los Angeles, CA, USA.
  • Lusis AJ; Department of Medicine, Division of Cardiology, David Geffen School of Medicine, Los Angeles, CA, USA.
  • Xu XZS; Life 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.
  • Li S; 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.
  • Yu Y; Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
  • Li JZ; Department of Human Genetics, University of Michigan Medical Center, Ann Arbor, MI 48109, USA.
  • Lin JD; 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. Electronic address: jdlin@umich.edu.
Mol Cell ; 75(3): 644-660.e5, 2019 08 08.
Article em En | MEDLINE | ID: mdl-31398325
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.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Comunicação Celular / Análise de Sequência de RNA / Hepatopatia Gordurosa não Alcoólica / Fígado Limite: Animals / Humans Idioma: En Ano de publicação: 2019 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Comunicação Celular / Análise de Sequência de RNA / Hepatopatia Gordurosa não Alcoólica / Fígado Limite: Animals / Humans Idioma: En Ano de publicação: 2019 Tipo de documento: Article