ArticleComparative hepatology2010
Expression of hepatocytic- and biliary-specific transcription factors in regenerating bile ducts during hepatocyte-to-biliary epithelial cell transdifferentiation.
Article in Comparative hepatology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
What it found
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Who cites it
16 citing papers in PubMed, 31 citations in OpenAlex.
- Reinterpreting the True Cause and Nature of Unexpected Liver Lumps.The American journal of pathology · 2025Article
- Update on Hepatobiliary Plasticity.Seminars in liver disease · 2023Article
- Characteristics of SOX9-positive progenitor-like cells during cholestatic liver regeneration in biliary atresia.Stem cell research & therapy · 2022Article
- Genomic characterization of rare molecular subclasses of hepatocellular carcinoma.Communications biology · 2021Article
- Review
- Stimulation of hepatocarcinogenesis by activated cholangiocytes via Il17a/f1 pathway in kras transgenic zebrafish model.Scientific reports · 2021Article
- Liver regeneration: biological and pathological mechanisms and implications.Nature reviews. Gastroenterology & hepatology · 2021Review
- Ductular reaction-on-a-chip: Microfluidic co-cultures to study stem cell fate selection during liver injury.Scientific reports · 2016Article
- Biliary fibrosis drives liver repopulation and phenotype transition of transplanted hepatocytes.Journal of hepatology · 2016Article
- Immunohistochemical characterization of the hepatic progenitor cell compartment in medaka (Oryzias latipes) following hepatic injury.Journal of comparative pathology · 2013Article
- Liver cancer: Intrahepatic cholangiocarcinoma--appearances can be deceiving.Nature reviews. Gastroenterology & hepatology · 2013Article
- Stem cells in liver diseases and cancer: recent advances on the path to new therapies.Hepatology (Baltimore, Md.) · 2012Review
- Fate tracing of mature hepatocytes in mouse liver homeostasis and regeneration.The Journal of clinical investigation · 2011Article
- Re-evaluation of liver stem/progenitor cells.OrganogenesisReview
- Bidirectional Mendelian randomization analysis reveals significant associations between Serum DNA repair proteins and liver cancer.Cancer biomarkers : section A of Disease markersArticle
- Immunohistochemical Analysis of the Stem Cell Marker LGR5 in Pediatric Liver Disease.Pediatric and developmental pathology : the official journal of the Society for Pediatric Pathology and the Paediatric Pathology SocietyArticle
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundUnder compromised biliary regeneration, transdifferentiation of hepatocytes into biliary epithelial cells (BEC) has been previously observed in rats, upon exposure to BEC-specific toxicant methylene dianiline (DAPM) followed by bile duct ligation (BDL), and in patients with chronic biliary liver disease. However, mechanisms promoting such transdifferentiation are not fully understood. In the present study, acquisition of biliary specific transcription factors by hepatocytes leading to reprogramming of BEC-specific cellular profile was investigated as a potential mechanism of transdifferentiation in two different models of compromised biliary regeneration in rats.
resultsIn addition to previously examined DAPM + BDL model, an experimental model resembling chronic biliary damage was established by repeated administration of DAPM. Hepatocyte to BEC transdifferentiation was tracked using dipetidyl dipeptidase IV (DDPIV) chimeric rats that normally carry DPPIV only in hepatocytes. Following DAPM treatment, ~20% BEC population turned DPPIV-positive, indicating that they are derived from DPPIV-positive hepatocytes. New ductules emerging after DAPM + BDL and repeated DAPM exposure expressed hepatocyte-associated transcription factor hepatocyte nuclear factor (HNF) 4α and biliary specific transcription factor HNF1β. In addition, periportal hepatocytes expressed biliary marker CK19 suggesting periportal hepatocytes as a potential source of transdifferentiating cells. Although TGFβ1 was induced, there was no considerable reduction in periportal HNF6 expression, as observed during embryonic biliary development.
conclusionsTaken together, these findings indicate that gradual loss of HNF4α and acquisition of HNF1β by hepatocytes, as well as increase in TGFβ1 expression in periportal region, appear to be the underlying mechanisms of hepatocyte-to-BEC transdifferentiation.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.