The DOI matches its Crossref record; 30 of the 30 references it cites were found in a registry or an index.
Cholangiocytes act as facultative liver stem cells during impaired hepatocyte regeneration
Open accessAbstract
After liver injury, regeneration occurs through self-replication of hepatocytes. In severe liver injury, hepatocyte proliferation is impaired-a feature of human chronic liver disease. It is unclear whether other liver cell types can regenerate hepatocytes. Here we use two independent systems to impair hepatocyte proliferation during liver injury to evaluate the contribution of non-hepatocytes to parenchymal regeneration. First, loss of β1-integrin in hepatocytes with liver injury triggered a ductular reaction of cholangiocyte origin, with approximately 25% of hepatocytes being derived from a non-hepatocyte origin. Second, cholangiocytes were lineage traced with concurrent inhibition of hepatocyte proliferation by β1-integrin knockdown or p21 overexpression, resulting in the significant emergence of cholangiocyte-derived hepatocytes. We describe a model of combined liver injury and inhibition of hepatocyte proliferation that causes physiologically significant levels of regeneration of functional hepatocytes from biliary cells.
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“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 [12]
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“The reprogramming of differentiated cells into progenitor-like cells has recently been discovered as an important injury-repair paradigm independent of adult stem cells in a variety of epithelial tissues in mammals, 1 such as the lung, 2 intestine, 3 pancreas, 4 and liver.5,6”
From Kupffer-cell-derived IL-6 is repurposed for hepatocyte dedifferentiation via activating progenitor genes from injury-specific enhancers (2023) · cites this paper as [5]
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Cites
Organoid Models and Applications in Biomedical Research
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In vitro expansion of single Lgr5+ liver stem cells induced by Wnt-driven regeneration
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Self-renewing diploid Axin2+ cells fuel homeostatic renewal of the liver
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A reproducible and well-tolerated method for 2/3 partial hepatectomy in mice
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Hybrid Periportal Hepatocytes Regenerate the Injured Liver without Giving Rise to Cancer
Font-Burgada, J., Shalapour, S., Ramaswamy, S., Hsueh, B., Rossell, D., Umemura, A., Taniguchi, K., Nakagawa, H., Valasek, M. A., Ye, L., et al. (2015) · Cell · doi:10.1016/j.cell.2015.07.026 · Cited by 486
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
Richardson, M. M., Jonsson, J. R., Powell, E. E., Brunt, E. M., Neuschwander–Tetri, B. A., Bhathal, P. S., Dixon, J. B., Weltman, M. D., Tilg, H., Moschen, A. R., et al. (2007) · Gastroenterology · doi:10.1053/j.gastro.2007.05.012 · Cited by 482
Hepatic progenitor cells of biliary origin with liver repopulation capacity
Lu, W.-Y., Bird, T. G., Boulter, L., Tsuchiya, A., Cole, A. M., Hay, T., Guest, R. V., Wojtacha, D., Man, T. Y., Mackinnon, A., et al. (2015) · Nature Cell Biology · doi:10.1038/ncb3203 · Cited by 479
Self-citationAdult Hepatocytes Are Generated by Self-Duplication Rather than Stem Cell Differentiation
Yanger, K., Knigin, D., Zong, Y., Maggs, L., Gu, G., Akiyama, H., Pikarsky, E., & Stanger, B. Z. (2014) · Cell Stem Cell · doi:10.1016/j.stem.2014.06.003 · Cited by 426
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Metadata
- Authors
- 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., Kotelevtsev, Y., ffrench-Constant, C., Boulter, L., & Forbes, S. J.
- Affiliations
- MRC Centre for Regenerative Medicine (GB)
- Institute of Genetics and Cancer (GB)
- Koch Institute for Integrative Cancer Research At MIT (US)
- Skolkovo Institute of Science and Technology (RU)
- Corresponding author
- Forbes, Stuart J.
- ORCID
- Venue
- Nature
- Published
- 2017-07-12
- Volume
- 547
- Issue
- 7663
- Pages
- 350-354
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC5522613
- OpenAlex
- W2734880494
- Cited by
- 533
- References
- 30
- Citations by year
- 2026: 32 · 2025: 47 · 2024: 47 · 2023: 62 · 2022: 56 · 2021: 80 · 2020: 79 · 2019: 62 · 2018: 61 · 2017: 7
- FWCI
- 35.32
- Type
- journal article
- Language
- en
- Update notices
- erratum (2018-03-15)
- Open access
- bronze
- doi.org
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- University of Birmingham Research Portal (University of Birmingham) (submittedVersion, other-oa)
- Edinburgh Research Explorer (University of Edinburgh) (submittedVersion, other-oa)
- UEA Digital Repository (University of East Anglia) (submittedVersion)
- Funders
- UK Regenerative Medicine Platform (K026666, MR/K026666/1, MR/L012766/1)
- Medical Research Council (MR/L012766/1, MR/K026666, MC_PC_U127574433, MR/K017047/1, MR/K026666/1)
- 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
- cholangiocytes, hepatocyte regeneration, liver injury, beta1 integrin, p21, cell cycle inhibition, ductular reaction, hepatocyte proliferation, chronic liver disease, lineage tracing
- MeSH terms
- Animals, Bile Ducts, Intrahepatic, Female, Liver, Liver Diseases, Liver Regeneration, Male, Mice, Inbred C57BL, Stem Cells, Integrin beta1, Cell Lineage, Hepatocytes, Cell Proliferation, Mice
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