ArticleStem cell research & therapy2022
Characteristics of SOX9-positive progenitor-like cells during cholestatic liver regeneration in biliary atresia.
Article in Stem cell research & therapy, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed.
- LncRNA H19 as a key regulator in biliary atresia: insights into pathogenesis and potential therapeutic targets.Annals of medicine · 2026Review
- PTEN-AKT2 regulates mixed lineage liver cancer development and sensitizes cancer cells to TGFβ treatment.Oncogene · 2026Article
- PTEN-AKT2 Regulates Mixed Lineage Liver Cancer Development and Sensitizes Cancer Cells to TGFβ Treatment.Research square · 2026Article
- Dynamic activation and dual roles of SOX9Frontiers in cell and developmental biology · 2026Article
- Anti-fibrotic effect of human amniotic fluid stem cells in biliary epithelial-mesenchymal transition of liver ductal organoid.Stem cells translational medicine · 2025Article
- Chromatin dynamics and regulatory drivers of hypoplastic hepatic progenitor cells in partial hepatectomy model.Communications biology · 2025Article
- Exosomes from liver progenitor cells carrying JAG1 activate notch signaling to promote liver regeneration in PVL rats.Cell death & disease · 2025Article
- Decoding Cellular Stress States for Toxicology Using Single-Cell Transcriptomics.bioRxiv : the preprint server for biology · 2025Article
- Multicomponent parenteral lipid emulsions do not prevent liver injury in neonatal pigs with obstructive cholestasis.JCI insight · 2025Article
- Single-cell transcription reveals hepatocyte-to-cholangiocyte reprogramming and biliary gene profile in biliary atresia.Hepatology communications · 2025Article
- Article
- SOX9: a key transcriptional regulator in organ fibrosis.Frontiers in pharmacology · 2025Review
- Hepatocyte differentiation requires anisotropic expansion of bile canaliculi.Development (Cambridge, England) · 2024Article
- Improvements in Maturity and Stability of 3D iPSC-Derived Hepatocyte-like Cell Cultures.Cells · 2023Article
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5 authors.
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Abstract
backgroundThe progression of Biliary Atresia (BA) is associated with the number of reactive ductular cells (RDCs) whose heterogeneity in origin and evolution in humans remains unknown. SOX9-positive liver progenitor-like cells (LPLCs) have been shown to participate in RDCs and new hepatocyte formation during cholestatic liver regeneration in an animal model, which implies the possibility that hepatocyte-reprogrammed LPLCs could be a source of RDCs in BA. The present study aimed to elucidate the characteristics of SOX9-positive LPLCs in BA for exploring new possible therapeutic targets by manipulating the bi-differentiation process of LPLCs to prevent disease progression.
methodsTwenty-eight patients, including 24 patients with BA and 4 patients with Congenital Choledochal Cyst as the control group, were retrospectively recruited. Liver biopsy samples were classified histologically using a 4-point scale based on fibrosis severity. LPLCs were detected by SOX9 and HNF4A double positive staining. Single immunohistochemistry, double immunohistochemistry, and multiple immunofluorescence staining were used to determine the different cell types and characteristics of LPLCs.
resultsThe prognostic predictors of BA, namely total bile acid (TBA), RDCs, and fibrosis, were correlated to the emergence of LPLCs. SOX9 and HNF4A double-positive LPLCs co-stained rarely with relevant markers of portal hepatic progenitor cells (portal-HPCs), including CK19, CK7, EPCAM, PROM1 (CD133), TROP2, and AFP. Under cholestasis conditions, LPLCs acquired superior proliferation and anti-senescence ability among hepatocytes. Moreover, LPLCs arranged as a pseudo-rosette structure appeared from the periportal parenchyma to the portal region, which implied the differentiation from hepatocyte-reprogrammed LPLCs to RDCs with the progression of cholestasis.
conclusionsLPLCs are associated with disease progression and prognostic factors of BA. The bipotent characteristics of LPLCs are different from those of portal-HPCs. As cholestasis progresses, LPLCs appear to gain superior proliferation and anti-senescence ability and continually differentiate to RDCs.
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