An atlas of the human liver diurnal transcriptome and its perturbation by hepatitis C virus infection. - Institut de recherche sur les maladies virales et hépatiques
Article Dans Une Revue Nature Communications Année : 2024

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

Yuji Teraoka
  • Fonction : Auteur

Résumé

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.
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hal-04699545 , version 1 (16-09-2024)

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Atish Mukherji, Frank Juehling, Yogy Simanjuntak, Emilie Crouchet, Fabio del Zompo, et al.. An atlas of the human liver diurnal transcriptome and its perturbation by hepatitis C virus infection.. Nature Communications, 2024, 15 (1), pp.7486. ⟨10.1038/s41467-024-51698-8⟩. ⟨hal-04699545⟩
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