Chronic Liver Injury Induces Conversion of Biliary Epithelial Cells into Hepatocytes
Open accessAbstract
Chronic liver injury can cause cirrhosis and impaired liver regeneration, impairing organ function. Adult livers can regenerate in response to parenchymal insults, and multiple cellular sources have been reported to contribute to this response. In this study, we modeled human chronic liver injuries, in which such responses are blunted, without genetic manipulations, and assessed potential contributions of non-parenchymal cells (NPCs) to hepatocyte regeneration. We show that NPC-derived hepatocytes replenish a large fraction of the liver parenchyma following severe injuries induced by long-term thioacetamide (TAA) or 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) treatment. Through lineage tracing of biliary epithelial cells (BECs), we show that BECs are a source of new hepatocytes and gain an Hnf4α+CK19+ bi-phenotypic state in periportal regions and fibrotic septa. Bi-phenotypic cells were also detected in cirrhotic human livers. Together, these data provide further support for hepatocyte regeneration from BECs without genetic interventions and show their cellular plasticity during severe liver injury.
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Hepatocyte replenishment can occur via conversion of cholangiocytes during severe liver injury.
“Hepatocyte replenishment can occur via conversion of cholangiocytes during severe liver injury12,13”
From Multimodal decoding of human liver regeneration (2024) · cites this paper as [13]
New hepatocytes from BEC transdifferentiation are reported to persist long-term and through chronic injury.
“and the new hepatocytes are reported to persist long-term and through chronic injury.113,119”
From Distinct hepatocyte identities in liver homeostasis and regeneration (2023) · cites this paper as [113]
When hepatocyte-mediated regeneration is impaired, following chronic injury and induction of hepatocyte senescence, BECs can transdifferentiate into zone 1 hepatocytes which subsequently proliferate and repopulate other lobular zones.
“When hepatocyte-mediated regeneration is impaired, following chronic injury and induction of hepatocyte senescence, BECs can transdifferentiate into zone 1 hepatocytes which subsequentially proliferate and repopulate other lobular zones[112], [113], [114], [115], [116], [117], [118]”
From Distinct hepatocyte identities in liver homeostasis and regeneration (2023) · cites this paper as [113]
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- Authors
- Deng, X., Zhang, X., Li, W., Feng, R.-X., Li, L., Yi, G.-R., Zhang, X.-N., Yin, C., Yu, H.-Y., Zhang, J.-P., Lu, B., Hui, L., & Xie, W.-F.
- Affiliations
- Second Military Medical University (CN)
- Chinese Academy of Sciences (CN)
- Corresponding author
- Hui, Lijian
- Xie, Wei-Fen
- Venue
- Cell Stem Cell
- Publisher
- Elsevier BV
- Published
- 2018-07
- Volume
- 23
- Issue
- 1
- Pages
- 114-122.e3
- ISSN
- 1875-9777 (ISSN-L)
- 1934-5909
- OpenAlex
- W2808974142
- Cited by
- 289
- References
- 21
- Citations by year
- 2026: 17 · 2025: 34 · 2024: 39 · 2023: 42 · 2022: 33 · 2021: 40 · 2020: 48 · 2019: 26 · 2018: 10
- FWCI
- 19.42
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell stem cell (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Natural Science Foundation of China (81530019, 30921006, 81521091, 31630044, 31501111, 81703093, 81772523)
- Shanghai Science and Technology Committee for the Key Projects (15JC1400200, 16JC1400202)
- External Cooperation Program of BIC, Chinese Academy of Science (XDA16020201, 153D31KYSB20150085)
- Topics
- Health Sciences › Medicine › Hepatology › Liver physiology and pathology
- Health Sciences › Medicine › Surgery › Tissue Engineering and Regenerative Medicine
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Drug-Induced Hepatotoxicity and Protection
- Keywords
- chronic liver injury, hepatocyte regeneration, cholangiocytes, cellular plasticity, non-parenchymal cells, liver cirrhosis, thioacetamide, DDC, lineage tracing, HNF4α, CK19, fibrosis
- MeSH terms
- Animals, Chronic Disease, Epithelial Cells, Humans, Liver Cirrhosis, Mice, Inbred Strains, Thioacetamide, Hepatocytes, Mice
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