1. Hepatitis C virus infects and perturbs liver stem cells
- Author
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Meyers, Nathan L, Ashuach, Tal, Lyons, Danielle E, Khalid, Mir M, Simoneau, Camille R, Erickson, Ann L, Bouhaddou, Mehdi, Nguyen, Thong T, Kumar, G Renuka, Taha, Taha Y, Natarajan, Vaishaali, Baron, Jody L, Neff, Norma, Zanini, Fabio, Mahmoudi, Tokameh, Quake, Stephen R, Krogan, Nevan J, Cooper, Stewart, McDevitt, Todd C, Yosef, Nir, and Ott, Melanie
- Subjects
Medical Microbiology ,Biomedical and Clinical Sciences ,Immunology ,Hepatitis - C ,Stem Cell Research - Induced Pluripotent Stem Cell - Human ,Stem Cell Research - Nonembryonic - Human ,Stem Cell Research ,Cancer ,Digestive Diseases ,Liver Disease ,Chronic Liver Disease and Cirrhosis ,Emerging Infectious Diseases ,Stem Cell Research - Nonembryonic - Non-Human ,Regenerative Medicine ,Genetics ,Stem Cell Research - Induced Pluripotent Stem Cell ,Biotechnology ,Infectious Diseases ,Hepatitis ,2.1 Biological and endogenous factors ,2.2 Factors relating to the physical environment ,Infection ,Good Health and Well Being ,hepatitis c virus ,organoid ,liver disease ,stem cell ,single-cell RNA sequencing ,chronic infection ,hepatocellular carcinoma ,Liver ,Organoids ,Hepatocytes ,Stem Cells ,Animals ,Humans ,Mice ,Hepacivirus ,Hepatitis C ,Microbiology ,Biochemistry and cell biology ,Medical microbiology - Abstract
ImportanceThe hepatitis C virus (HCV) causes liver disease, affecting millions. Even though we have effective antivirals that cure HCV, they cannot stop terminal liver disease. We used an adult stem cell-derived liver organoid system to understand how HCV infection leads to the progression of terminal liver disease. Here, we show that HCV maintains low-grade infections in liver organoids for the first time. HCV infection in liver organoids leads to transcriptional reprogramming causing cancer cell development and altered immune response. Our finding shows how HCV infection in liver organoids mimics HCV infection and patient pathogenesis. These results reveal that HCV infection in liver organoids contributes to liver disease progression.
- Published
- 2023