Self-maintenance of zonal hepatocytes during adult homeostasis and their complex plasticity upon distinct liver injuries
Summary: Hepatocytes are organized into distinct zonal subsets across the liver lobule, yet their contributions to liver homeostasis and regeneration remain controversial. Here, we developed multiple genetic lineage-tracing mouse models to systematically address this. We found that the liver lobule...
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Elsevier
2025-01-01
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| Series: | Cell Reports |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S221112472401444X |
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| author | Chow Hiang Ang Philip Arandjelovic Jinming Cheng Jicheng Yang Fusheng Guo Yuanquan Yu Sarmilla Nelameham Lachlan Whitehead Jiangtao Li David L. Silver Nick Barker Jane E. Visvader Pierce K.H. Chow Gordon K. Smyth Yunshun Chen David M. Virshup Nai Yang Fu |
| author_facet | Chow Hiang Ang Philip Arandjelovic Jinming Cheng Jicheng Yang Fusheng Guo Yuanquan Yu Sarmilla Nelameham Lachlan Whitehead Jiangtao Li David L. Silver Nick Barker Jane E. Visvader Pierce K.H. Chow Gordon K. Smyth Yunshun Chen David M. Virshup Nai Yang Fu |
| author_sort | Chow Hiang Ang |
| collection | DOAJ |
| description | Summary: Hepatocytes are organized into distinct zonal subsets across the liver lobule, yet their contributions to liver homeostasis and regeneration remain controversial. Here, we developed multiple genetic lineage-tracing mouse models to systematically address this. We found that the liver lobule can be divided into two major zonal and molecular hepatocyte populations marked by Cyp2e1 or Gls2. Pericentral Cyp2e1+ and periportal Gls2+ hepatocytes maintain their own lineage during adult homeostasis, while Cyp2e1+ hepatocytes fuel neonatal liver growth. The Gls2+ and Cyp2e1+ populations can rapidly regenerate one another when one of the populations is severely damaged. Midlobular Ccnd1+ hepatocytes are enriched in the Cyp2e1+ zone in adult liver but have limited contributions to regeneration upon partial hepatectomy and severe pericentral injury. Remarkably, Lgr5+ hepatocytes, a unique Cyp2e1+ subset, contribute significantly to liver replenishment upon periportal injuries. Our findings unravel that zonal hepatocytes mainly self-maintain during homeostasis but exhibit complex plasticity in repair upon injury. |
| format | Article |
| id | doaj-art-4e966f936e67499dbfbea9724c260f37 |
| institution | OA Journals |
| issn | 2211-1247 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj-art-4e966f936e67499dbfbea9724c260f372025-08-20T01:57:21ZengElsevierCell Reports2211-12472025-01-0144111509310.1016/j.celrep.2024.115093Self-maintenance of zonal hepatocytes during adult homeostasis and their complex plasticity upon distinct liver injuriesChow Hiang Ang0Philip Arandjelovic1Jinming Cheng2Jicheng Yang3Fusheng Guo4Yuanquan Yu5Sarmilla Nelameham6Lachlan Whitehead7Jiangtao Li8David L. Silver9Nick Barker10Jane E. Visvader11Pierce K.H. Chow12Gordon K. Smyth13Yunshun Chen14David M. Virshup15Nai Yang Fu16Cancer and Stem Cell Biology Program, Duke-NUS Medical School, Singapore 169857, SingaporeCancer Biology and Stem Cells Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia; Department of Medical Biology, University of Melbourne, Parkville, VIC 3010, AustraliaCancer Biology and Stem Cells Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia; Department of Medical Biology, University of Melbourne, Parkville, VIC 3010, Australia; Bioinformatics Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, AustraliaCancer and Stem Cell Biology Program, Duke-NUS Medical School, Singapore 169857, Singapore; Cancer Biology and Stem Cells Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia; Department of Medical Biology, University of Melbourne, Parkville, VIC 3010, AustraliaCancer and Stem Cell Biology Program, Duke-NUS Medical School, Singapore 169857, SingaporeHPB Surgery, The Second Affiliated Hospital Zhejiang University School of Medicine, Hangzhou, ChinaCancer and Stem Cell Biology Program, Duke-NUS Medical School, Singapore 169857, SingaporeDepartment of Medical Biology, University of Melbourne, Parkville, VIC 3010, Australia; Advanced Technology and Biology Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, AustraliaHPB Surgery, The Second Affiliated Hospital Zhejiang University School of Medicine, Hangzhou, ChinaCardiovascular & Metabolic Disorders Program, Duke-NUS Medical School, Singapore 169857, SingaporeInstitute of Molecular and Cell Biology, Agency for Science, Technology, and Research (A∗STAR), Singapore 138673, Singapore; Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, SingaporeCancer Biology and Stem Cells Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia; Department of Medical Biology, University of Melbourne, Parkville, VIC 3010, AustraliaSurgery Academic-Clinical Program, Duke-NUS Medical School, Singapore 169857, Singapore; Department of Hepato-pancreato-biliary and Transplant Surgery, Division of Surgery and Surgical Oncology, Singapore General Hospital and National Cancer Centre Singapore, SingaporeBioinformatics Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia; School of Mathematics and Statistics, University of Melbourne, Parkville, VIC 3010, AustraliaCancer Biology and Stem Cells Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia; Department of Medical Biology, University of Melbourne, Parkville, VIC 3010, Australia; Bioinformatics Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, AustraliaCancer and Stem Cell Biology Program, Duke-NUS Medical School, Singapore 169857, SingaporeCancer and Stem Cell Biology Program, Duke-NUS Medical School, Singapore 169857, Singapore; Cancer Biology and Stem Cells Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia; Department of Medical Biology, University of Melbourne, Parkville, VIC 3010, Australia; Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore; Corresponding authorSummary: Hepatocytes are organized into distinct zonal subsets across the liver lobule, yet their contributions to liver homeostasis and regeneration remain controversial. Here, we developed multiple genetic lineage-tracing mouse models to systematically address this. We found that the liver lobule can be divided into two major zonal and molecular hepatocyte populations marked by Cyp2e1 or Gls2. Pericentral Cyp2e1+ and periportal Gls2+ hepatocytes maintain their own lineage during adult homeostasis, while Cyp2e1+ hepatocytes fuel neonatal liver growth. The Gls2+ and Cyp2e1+ populations can rapidly regenerate one another when one of the populations is severely damaged. Midlobular Ccnd1+ hepatocytes are enriched in the Cyp2e1+ zone in adult liver but have limited contributions to regeneration upon partial hepatectomy and severe pericentral injury. Remarkably, Lgr5+ hepatocytes, a unique Cyp2e1+ subset, contribute significantly to liver replenishment upon periportal injuries. Our findings unravel that zonal hepatocytes mainly self-maintain during homeostasis but exhibit complex plasticity in repair upon injury.http://www.sciencedirect.com/science/article/pii/S221112472401444XCP: Stem cell research |
| spellingShingle | Chow Hiang Ang Philip Arandjelovic Jinming Cheng Jicheng Yang Fusheng Guo Yuanquan Yu Sarmilla Nelameham Lachlan Whitehead Jiangtao Li David L. Silver Nick Barker Jane E. Visvader Pierce K.H. Chow Gordon K. Smyth Yunshun Chen David M. Virshup Nai Yang Fu Self-maintenance of zonal hepatocytes during adult homeostasis and their complex plasticity upon distinct liver injuries Cell Reports CP: Stem cell research |
| title | Self-maintenance of zonal hepatocytes during adult homeostasis and their complex plasticity upon distinct liver injuries |
| title_full | Self-maintenance of zonal hepatocytes during adult homeostasis and their complex plasticity upon distinct liver injuries |
| title_fullStr | Self-maintenance of zonal hepatocytes during adult homeostasis and their complex plasticity upon distinct liver injuries |
| title_full_unstemmed | Self-maintenance of zonal hepatocytes during adult homeostasis and their complex plasticity upon distinct liver injuries |
| title_short | Self-maintenance of zonal hepatocytes during adult homeostasis and their complex plasticity upon distinct liver injuries |
| title_sort | self maintenance of zonal hepatocytes during adult homeostasis and their complex plasticity upon distinct liver injuries |
| topic | CP: Stem cell research |
| url | http://www.sciencedirect.com/science/article/pii/S221112472401444X |
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