ArticleThe Journal of biological chemistry2014
Sry HMG box protein 9-positive (Sox9+) epithelial cell adhesion molecule-negative (EpCAM-) biphenotypic cells derived from hepatocytes are involved in mouse liver regeneration.
Article in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 69 papers.
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Who cites it
69 citing papers in PubMed, 106 citations in OpenAlex.
- Mesenchymal stromal cell administration promotes macrophage-mediated bile duct regeneration.Regenerative therapy · 2026Article
- Expansion of human hepatocytes and their application in three-dimensional culture and genetic manipulation.Nature protocols · 2025Article
- Plastic hepatocyte states limit liver cancer development.Nature communications · 2025Article
- Organ-Specific Dedifferentiation and Epigenetic Remodeling in In Vivo Reprogramming.Aging cell · 2025Review
- Chromatin dynamics and regulatory drivers of hypoplastic hepatic progenitor cells in partial hepatectomy model.Communications biology · 2025Article
- Expression of DNAJB1-PRKACA oncogene suppresses the differentiation potential of liver progenitor organoids towards a hepatocyte lineage.Scientific reports · 2025Article
- Lineage plasticity and reprogramming of epithelial cells during tissue injury and regeneration-lessons from the lineage plasticity of hepatocytes and cholangiocytes induced by liver injury.Regenerative therapy · 2025Review
- Aberrant differentiation and proliferation of hepatocytes in chronic liver injury and liver tumors.Pathology international · 2024Review
- Neutrophil and macrophage crosstalk might be a potential target for liver regeneration.FEBS open bio · 2024Article
- Transcriptional Control: A Directional Sign at the Crossroads of Adult Hepatic Progenitor Cells' Fates.International journal of biological sciences · 2024Review
- Hepatocyte dedifferentiation profiling in alcohol-related liver disease identifies CXCR4 as a driver of cell reprogramming.Journal of hepatology · 2023Article
- Distinct hepatocyte identities in liver homeostasis and regeneration.JHEP reports : innovation in hepatology · 2023Review
- Review
- Small molecule drugs promote repopulation of transplanted hepatocytes by stimulating cell dedifferentiation.JHEP reports : innovation in hepatology · 2023Article
- Biliary epithelial cell differentiation of bipotent human liver-derived organoids by 2D and 3D culture.Biochemistry and biophysics reports · 2023Article
- Multiple Facets of Cellular Homeostasis and Regeneration of the Mammalian Liver.Annual review of physiology · 2023Review
- Dynamics of hepatocyte-cholangiocyte cell-fate decisions during liver development and regeneration.iScience · 2022Article
- Notch-Sox9 Axis Mediates Hepatocyte Dedifferentiation inInternational journal of molecular sciences · 2022Article
- LPS/Bcl3/YAP1 signaling promotes Sox9Cell death & disease · 2022Article
- Characteristics of SOX9-positive progenitor-like cells during cholestatic liver regeneration in biliary atresia.Stem cell research & therapy · 2022Article
9 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
It has been shown that mature hepatocytes compensate tissue damages not only by proliferation and/or hypertrophy but also by conversion into cholangiocyte-like cells. We found that Sry HMG box protein 9-positive (Sox9(+)) epithelial cell adhesion molecule-negative (EpCAM(-)) hepatocyte nuclear factor 4α-positive (HNF4α(+)) biphenotypic cells showing hepatocytic morphology appeared near EpCAM(+) ductular structures in the livers of mice fed 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC)-containing diet. When Mx1-Cre:ROSA mice, which were injected with poly(I:C) to label mature hepatocytes, were fed with the DDC diet, we found LacZ(+)Sox9(+) cells near ductular structures. Although Sox9(+)EpCAM(-) cells adjacent to expanding ducts likely further converted into ductular cells, the incidence was rare. To know the cellular characteristics of Sox9(+)EpCAM(-) cells, we isolated them as GFP(+)EpCAM(-) cells from DDC-injured livers of Sox9-EGFP mice. Sox9(+)EpCAM(-) cells proliferated and could differentiate to functional hepatocytes in vitro. In addition, Sox9(+)EpCAM(-) cells formed cysts with a small central lumen in collagen gels containing Matrigel® without expressing EpCAM. These results suggest that Sox9(+)EpCAM(-) cells maintaining biphenotypic status can establish cholangiocyte-type polarity. Interestingly, we found that some of the Sox9(+) cells surrounded luminal spaces in DDC-injured liver while they expressed HNF4α. Taken together, we consider that in addition to converting to cholangiocyte-like cells, Sox9(+)EpCAM(-) cells provide luminal space near expanded ductular structures to prevent deterioration of the injuries and potentially supply new hepatocytes to repair damaged tissues.
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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.