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ArticleCellular and molecular gastroenterology and hepatology2026

Pbrm1 Loss Induces a Permissive Chromatin State for Cholangiocytic Differentiation and Cholangiocarcinoma Formation.

Li-Wen Chiou, Yu-Lin Jhuang, Chia-Lang Hsu, Ray-Hwang Yuan, Yen-Hsu Cheng, Chia-Hsiang Lee, Yi-Ting Fang, Ching-Yao Yang, Yung-Ming Jeng

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Article in Cellular and molecular gastroenterology and hepatology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

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2citing papers in PubMed
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1 · What the graph read from it

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3 · Its place in the literature

Who cites it

2 citing papers in PubMed.

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4 · The record

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5 · Who and what money

Authors and funding

9 authors.

Li-Wen ChiouGraduate Institute of Pathology, National Taiwan University, Taipei, Taiwan; Department of Pathology, National Taiwan University Hospital, Taipei, Taiwan.
Yu-Lin JhuangGraduate Institute of Pathology, National Taiwan University, Taipei, Taiwan; Department of Pathology, National Taiwan University Hospital, Taipei, Taiwan.
Chia-Lang HsuDepartment of Medical Research, National Taiwan University Hospital, Taipei, Taiwan.
Ray-Hwang YuanDepartment of Surgery, National Taiwan University Hospital, Taipei, Taiwan; Department of Surgery, National Taiwan University Hospital, Hsinchu Branch, Hsinchu, Taiwan.
Yen-Hsu ChengGraduate Institute of Pathology, National Taiwan University, Taipei, Taiwan; Department of Pathology, National Taiwan University Hospital, Taipei, Taiwan.
Chia-Hsiang LeeDepartment of Pathology, National Taiwan University Hospital, Taipei, Taiwan.
Yi-Ting FangDepartment of Pathology, National Taiwan University Hospital, Taipei, Taiwan.
Ching-Yao YangDepartment of Surgery, National Taiwan University Hospital, Taipei, Taiwan.
Yung-Ming JengGraduate Institute of Pathology, National Taiwan University, Taipei, Taiwan; Department of Pathology, National Taiwan University Hospital, Taipei, Taiwan. Electronic address: mrna0912@gmail.com.tw.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

BACKGROUND &

aimsThe SWI/SNF ATP-dependent chromatin remodeling complex regulates transcriptional machinery access and is critical in normal physiology and cancer development. PBRM1, a key subunit of this complex, is frequently mutated in intrahepatic cholangiocarcinoma (iCCA). This study aims to explore the role of PBRM1 in liver physiology and its involvement in iCCA development.

methodsLiver-specific Pbrm1 knockout (Pbrm1 KO) mice were generated to assess the effects of Pbrm1 loss under various conditions. These mice were exposed to a 3,5-diethoxycarbonyl-1,4-dihydrocollidine diet to induce cholestatic injury and were also subjected to a high-fat diet to evaluate susceptibility to liver steatosis. Chromatin accessibility and gene expression under both normal and injury conditions were examined. Additionally, the impact of Pbrm1 loss was analyzed in combination with an activating Kras

resultsPbrm1 KO mice exhibited increased susceptibility to cholestatic injury, with an enhanced ductular reaction. Loss of Pbrm1 reduced chromatin accessibility at hepatocyte-specific and metabolically important genes, although RNA expression remained unaffected during homeostasis. Following cholestatic injury, hepatocyte-specific gene expression was significantly reduced compared with wild-type controls. Pbrm1 KO mice also showed heightened vulnerability to high-fat diet-induced liver steatosis. When combined with Kras

conclusionsPBRM1 maintains chromatin accessibility for hepatocyte differentiation-related genes. Its loss promotes differentiation toward cholangiocytes during injury or tumorigenesis, driving iCCA development.

Indexed as

Bile Duct NeoplasmsCholangiocarcinomaChromatinDNA-Binding ProteinsNuclear ProteinsTranscription FactorsAnimalsCell DifferentiationCholestasisChromatin Assembly and DisassemblyDiet, High-FatDisease Models, AnimalHumansLiverMaleMice3,5-diethoxycarbonyl-1,4-dihydrocollidineChromatinDNA-Binding ProteinsNuclear ProteinsPyridinesTranscription FactorsCell FateChromatin RemodelingKnockout MiceSNF/SWI Complex

Identifiers

PMID41513002
PMCPMC12995892

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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.