Transdifferentiation of rat hepatocytes into biliary cells after bile duct ligation and toxic biliary injury†
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Rats with chimeric livers were generated by using the protocol of injecting hepatocytes from dipeptidyl peptidase IV (DPPIV)-positive donors into retrorsine-treated DPPIV-negative recipients subjected to partial hepatectomy. Rats with established chimeric livers were subjected to bile duct ligation, with or without pretreatment with the biliary toxin methylene diamiline (DAPM). Ductules bearing the donor hepatocyte marker DPPIV were seen at 30 days after bile duct ligation. The frequency of the ductules derived from the donor hepatocytes was dramatically enhanced (36-fold) by the pretreatment with DAPM. In conclusion, our results show that hepatocytes can function as facultative stem cells and rescue the biliary epithelium during repair from injury when its proliferative capacity is being compromised.
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Hepatocytes display remarkable plasticity and under some conditions can transdifferentiate into BECs.
“Hepatocytes display remarkable plasticity and under some conditions can transdifferentiate into BECs, epithelial cells of the bile ducts with completely different morphology, gene expression and function59,[97], [98], [99]”
From Distinct hepatocyte identities in liver homeostasis and regeneration (2023) · cites this paper as [97]
Lineage-tracing studies in animal models have confirmed that hepatocytes contribute to bile duct remodeling following cholangiocyte injury.
“Lineage-tracing studies in animal models have confirmed that hepatocytes contribute to bile duct remodeling following cholangiocyte injury10,43–48”
From HBO1 functions as an epigenetic barrier to hepatocyte plasticity and reprogramming during liver injury (2025) · cites this paper as [47]
Transdifferentiation of hepatocytes into biliary ductules is damage dependent and negligible unless significant injury is induced.
“The transdifferentiation of hepatocytes into biliary ductules is damage dependent and negligible unless significant injury is induced26.”
From Hepatic progenitor cells of biliary origin with liver repopulation capacity (2015) · cites this paper as [26]
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- Authors
- Michalopoulos, G. K., Barua, L., & Bowen, W. C.
- Affiliations
- University of Pittsburgh (US)
- Corresponding author
- Michalopoulos, George K.
- Venue
- Hepatology
- Published
- 2005-03
- Volume
- 41
- Issue
- 3
- Pages
- 535-544
- ISSN
- 0270-9139 (ISSN-L)
- PMC
- PMC1821079
- OpenAlex
- W2092743512
- Cited by
- 319
- References
- 48
- Citations by year
- 2026: 8 · 2025: 7 · 2024: 12 · 2023: 16 · 2022: 12 · 2021: 22 · 2020: 24 · 2019: 18 · 2018: 20 · 2017: 16 · 2016: 17 · 2015: 21 · 2014: 23 · 2013: 19 · 2012: 18
- FWCI
- 8.85
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Hepatology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (2r01ca103958-06a1)
- National Cancer Institute (CA 35373, R01CA035373, R01-CA103958, CA103958)
- Topics
- Health Sciences › Medicine › Hepatology › Liver physiology and pathology
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Drug-Induced Hepatotoxicity and Protection
- Health Sciences › Medicine › Surgery › Organ Transplantation Techniques and Outcomes
- Keywords
- hepatocyte transdifferentiation, bile duct ligation, biliary injury, dipeptidyl peptidase IV, partial hepatectomy
- MeSH terms
- Aniline Compounds, Animals, Benzhydryl Compounds, Bile Ducts, Biliary Tract, Cell Differentiation, Epithelial Cells, Ligation, Liver Regeneration, Male, Rats, Inbred F344, Dipeptidyl Peptidase 4, Hepatocytes, Cell Proliferation, Rats
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