The DOI matches its Crossref record; 20 of the 21 references it cites were found in a registry or an index.
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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In the citing paper
“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]
In the citing paper
“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]
In the citing paper
“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]
Citations
Cites
Bataller, R., & Brenner, D. A. (2005) · Journal of Clinical Investigation · doi:10.1172/jci24282 · Cited by 4,958
A global double-fluorescent Cre reporter mouse
Muzumdar, M. D., Tasic, B., Miyamichi, K., Li, L., & Luo, L. (2007) · genesis · doi:10.1002/dvg.20335 · Cited by 3,491
Self-citationSchuppan, D., & Afdhal, N. H. (2008) · The Lancet · doi:10.1016/s0140-6736(08)60383-9 · Cited by 2,089
Michalopoulos, G. K. (2007) · Journal of Cellular Physiology · doi:10.1002/jcp.21172 · Cited by 1,384
Kretzschmar, K., & Watt, F. M. (2012) · Cell · doi:10.1016/j.cell.2012.01.002 · Cited by 756
Liver regeneration and repair: Hepatocytes, progenitor cells, and stem cells
Fausto, N. (2004) · Hepatology · doi:10.1002/hep.20214 · Cited by 720
Evolving challenges in hepatic fibrosis
Friedman, S. L. (2010) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/nrgastro.2010.97 · Cited by 590
Bipotential Adult Liver Progenitors Are Derived from Chronically Injured Mature Hepatocytes
Tarlow, B. D., Pelz, C., Naugler, W. E., Wakefield, L., Wilson, E. M., Finegold, M. J., & Grompe, M. (2014) · Cell Stem Cell · doi:10.1016/j.stem.2014.09.008 · Cited by 533
Cholangiocytes act as facultative liver stem cells during impaired hepatocyte regeneration
Raven, A., Lu, W.-Y., Man, T. Y., Ferreira-Gonzalez, S., O’Duibhir, E., Dwyer, B. J., Thomson, J. P., Meehan, R. R., Bogorad, R., Koteliansky, V., et al. (2017) · Nature · doi:10.1038/nature23015 · Cited by 533
Robust cellular reprogramming occurs spontaneously during liver regeneration
Yanger, K., Zong, Y., Maggs, L. R., Shapira, S. N., Maddipati, R., Aiello, N. M., Thung, S. N., Wells, R. G., Greenbaum, L. E., & Stanger, B. Z. (2013) · Genes & Development · doi:10.1101/gad.207803.112 · Cited by 484
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1 of the 21 references couldn’t be matched to a known paper.
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Liver regeneration: biological and pathological mechanisms and implications
Michalopoulos, G. K., & Bhushan, B. (2021) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/s41575-020-0342-4 · Cited by 998
Liver organoids: from basic research to therapeutic applications
Prior, N., Inacio, P., & Huch, M. (2019) · Gut · doi:10.1136/gutjnl-2019-319256 · Cited by 356
Building consensus on definition and nomenclature of hepatic, pancreatic, and biliary organoids
Marsee, A., Roos, F. J. M., Verstegen, M. M. A., Marsee, A., Roos, F., Verstegen, M., Clevers, H., Vallier, L., Takebe, T., Huch, M., et al. (2021) · Cell Stem Cell · doi:10.1016/j.stem.2021.04.005 · Cited by 310
Liver homeostasis is maintained by midlobular zone 2 hepatocytes
Wei, Y., Wang, Y. G., Jia, Y., Li, L., Yoon, J., Zhang, S., Wang, Z., Zhang, Y., Zhu, M., Sharma, T., et al. (2021) · Science · doi:10.1126/science.abb1625 · Cited by 292
Self-citationSaviano, A., Henderson, N. C., & Baumert, T. F. (2020) · Journal of Hepatology · doi:10.1016/j.jhep.2020.06.004 · Cited by 276
Metadata
- 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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