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An atlas of the human liver diurnal transcriptome and its perturbation by hepatitis C virus infection

Author

Listed:
  • Atish Mukherji

    (Institute of Translational Medicine and Liver Diseases (ITM))

  • Frank Jühling

    (Institute of Translational Medicine and Liver Diseases (ITM))

  • Yogy Simanjuntak

    (Institute of Translational Medicine and Liver Diseases (ITM))

  • Emilie Crouchet

    (Institute of Translational Medicine and Liver Diseases (ITM))

  • Fabio Zompo

    (Institute of Translational Medicine and Liver Diseases (ITM))

  • Yuji Teraoka

    (National Hospital Organization Kure Medical Center)

  • Alexandre Haller

    (CNRS/INSERM/University of Strasbourg)

  • Philippe Baltzinger

    (CNRS/INSERM/University of Strasbourg)

  • Soumith Paritala

    (University of Texas Southwestern Medical Center)

  • Fahmida Rasha

    (University of Texas Southwestern Medical Center)

  • Naoto Fujiwara

    (University of Texas Southwestern Medical Center)

  • Cloé Gadenne

    (Institute of Translational Medicine and Liver Diseases (ITM))

  • Nevena Slovic

    (Institute of Translational Medicine and Liver Diseases (ITM))

  • Marine A. Oudot

    (Institute of Translational Medicine and Liver Diseases (ITM))

  • Sarah C. Durand

    (Institute of Translational Medicine and Liver Diseases (ITM))

  • Clara Ponsolles

    (Institute of Translational Medicine and Liver Diseases (ITM))

  • Catherine Schuster

    (Institute of Translational Medicine and Liver Diseases (ITM))

  • Xiaodong Zhuang

    (University of Oxford
    Division of Infection & Immunity, UCL, Pears Building)

  • Jacinta Holmes

    (St Vincent’s Hospital)

  • Ming-Lun Yeh

    (Kaohsiung Medical University)

  • Hiromi Abe-Chayama

    (Center for Medical Specialist Graduate Education and Research, Hiroshima University)

  • Mathias Heikenwälder

    (German Cancer Research Center (DKFZ)
    ” Eberhard-Karls University of Tübingen)

  • Angelo Sangiovanni

    (Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico)

  • Massimo Iavarone

    (Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico)

  • Massimo Colombo

    (EASL International Liver Foundation)

  • Steven K. H. Foung

    (Stanford University School of Medicine)

  • Jane A. McKeating

    (University of Oxford
    University of Oxford)

  • Irwin Davidson

    (CNRS/INSERM/University of Strasbourg)

  • Ming-Lung Yu

    (Kaohsiung Medical University
    National Sun Yat-sen University)

  • Raymond T. Chung

    (Massachusetts General Hospital)

  • Yujin Hoshida

    (University of Texas Southwestern Medical Center)

  • Kazuaki Chayama

    (RIKEN Center for Integrative Medical Sciences
    Hiroshima Institute of Life Sciences)

  • Joachim Lupberger

    (Institute of Translational Medicine and Liver Diseases (ITM))

  • Thomas F. Baumert

    (Institute of Translational Medicine and Liver Diseases (ITM)
    Strasbourg University Hospitals
    Institut Universitaire de France
    IHU)

Abstract

Chronic liver disease and cancer are global health challenges. The role of the circadian clock as a regulator of liver physiology and disease is well established in rodents, however, the identity and epigenetic regulation of rhythmically expressed genes in human disease is less well studied. Here we unravel the rhythmic transcriptome and epigenome of human hepatocytes using male human liver chimeric mice. We identify a large number of rhythmically expressed protein coding genes in human hepatocytes of male chimeric mice, which includes key transcription factors, chromatin modifiers, and critical enzymes. We show that hepatitis C virus (HCV) infection, a major cause of liver disease and cancer, perturbs the transcriptome by altering the rhythmicity of the expression of more than 1000 genes, and affects the epigenome, leading to an activation of critical pathways mediating metabolic alterations, fibrosis, and cancer. HCV-perturbed rhythmic pathways remain dysregulated in patients with advanced liver disease. Collectively, these data support a role for virus-induced perturbation of the hepatic rhythmic transcriptome and pathways in cancer development and may provide opportunities for cancer prevention and biomarkers to predict HCC risk.

Suggested Citation

  • Atish Mukherji & Frank Jühling & Yogy Simanjuntak & Emilie Crouchet & Fabio Zompo & Yuji Teraoka & Alexandre Haller & Philippe Baltzinger & Soumith Paritala & Fahmida Rasha & Naoto Fujiwara & Cloé Gad, 2024. "An atlas of the human liver diurnal transcriptome and its perturbation by hepatitis C virus infection," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
  • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-51698-8
    DOI: 10.1038/s41467-024-51698-8
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    References listed on IDEAS

    as
    1. Xiaodong Zhuang & Donall Forde & Senko Tsukuda & Valentina D’Arienzo & Laurent Mailly & James M. Harris & Peter A. C. Wing & Helene Borrmann & Mirjam Schilling & Andrea Magri & Claudia Orbegozo Rubio , 2021. "Circadian control of hepatitis B virus replication," Nature Communications, Nature, vol. 12(1), pages 1-13, December.
    2. Miaomiao Sun & Wenting Feng & Feng Wang & Liuzhuo Zhang & Zijun Wu & Zhimin Li & Bo Zhang & Yonghua He & Shaohua Xie & Mengjie Li & Joan P C Fok & Gary Tse & Martin C S Wong & Jin-ling Tang & Samuel Y, 2018. "Night shift work exposure profile and obesity: Baseline results from a Chinese night shift worker cohort," PLOS ONE, Public Library of Science, vol. 13(5), pages 1-14, May.
    3. Emilie Crouchet & Simonetta Bandiera & Naoto Fujiwara & Shen Li & Hussein El Saghire & Mirian Fernández-Vaquero & Tobias Riedl & Xiaochen Sun & Hadassa Hirschfield & Frank Jühling & Shijia Zhu & Natas, 2021. "A human liver cell-based system modeling a clinical prognostic liver signature for therapeutic discovery," Nature Communications, Nature, vol. 12(1), pages 1-19, December.
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