ArticleCell reports2023
Genome-wide profiling of transcription factor activity in primary liver cancer using single-cell ATAC sequencing.
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Article in Cell reports, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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23 citing papers in PubMed, 26 citations in OpenAlex.
- Inhibition of PERK signaling suppresses tumor progression and blocks GP73-GRP78-dependent stromal activation in hepatocellular carcinoma.Neoplasia (New York, N.Y.) · 2026Article
- How to efficiently establish animal models of cholangiocarcinoma: challenges and inspiration.Medical review (2021) · 2026Review
- A generic reference defined by consensus peaks for single-cell ATAC-seq data analysis.Nature communications · 2026Article
- Multimodal-based analysis of single-cell ATAC-seq data enables highly accurate delineation of clinically relevant tumor cell subpopulations.Genome medicine · 2026Article
- Functional Interpretation of Recurrent Genetic Variants in Hepatocellular Carcinoma: Molecular Consequences and Clinical Relevance.Human mutation · 2026Review
- AI-integrated single-cell multi-omics decodes the hepatocellular carcinoma metabolism-immune axis: a new strategy for precision therapeutic targeting.Frontiers in oncology · 2026Review
- FOXP1-transcriptionally regulated AEG-1 enhances tumor cell stemness to promote hepatocellular carcinoma radioresistance.Molecular and cellular biochemistry · 2026Article
- Single-cell multi-omics analysis reveals cancer regulatory elements of transcriptional programs and clinical implications.Cell death & disease · 2025Article
- Short-chain acyl post-translational modifications in cancers: Mechanisms, roles, and therapeutic implications.Cancer communications (London, England) · 2025Review
- Immune microenvironment in hepatocellular carcinoma: from pathogenesis to immunotherapy.Cellular & molecular immunology · 2025Review
- CRISPR screening reveals that RNA helicase DDX41 triggers ribosome biogenesis and cancer progression through R-loop-mediated RPL/RPS transcription.Nature communications · 2025Article
- Clonorchis sinensis infection remodels chromatin accessibility in hepatocellular carcinoma.Parasites & vectors · 2025Article
- Chromatin accessibility module identified by single-cell sequencing underlies the diagnosis and prognosis of hepatocellular carcinoma.World journal of hepatology · 2025Article
- BIT: Bayesian Identification of Transcriptional regulators from epigenomics-based query region sets.Nature communications · 2025Article
- Bisphenol S Exposure and MASLD: A Mechanistic Study in Mice.Environmental health perspectives · 2025Article
- Morphomolecular Pathology and Genomic Insights into the Cells of Origin of Cholangiocarcinoma and Combined Hepatocellular-Cholangiocarcinoma.The American journal of pathology · 2025Review
- Targeting super-enhancers in liver cancer: from pathogenic mechanisms to clinical applications.Frontiers in pharmacology · 2025Review
- Chromatin accessibility: biological functions, molecular mechanisms and therapeutic application.Signal transduction and targeted therapy · 2024Review
- EpiCHAOS: a metric to quantify epigenomic heterogeneity in single-cell data.Genome biology · 2024Article
- Characterization of cell states in biliary tract cancers identifies mechanisms of therapeutic resistance in a phase II trial of DKN-01/nivolumab.medRxiv : the preprint server for health sciences · 2024Article
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Authors and funding
24 authors at 6 institutions in 3 countries.
Amanda J CraigLaboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA.
Maruhen A Datsch SilveiraLaboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA.
Lichun MaLaboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA; Cancer Data Science Laboratory, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA; Liver Cancer Program, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA.
Mahler RevsineLaboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA.
Limin WangLaboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA.
Sophia HeinrichLaboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA; Department of Gastroenterology, Hepatology, Infectious Diseases and Endocrinology, Hanover Medical School, 30159 Hanover, Germany.
Zachary RaeFrederick National Laboratory for Cancer Research, Leidos Biomedical Research, Inc., Frederick, MD 20701, USA.
Allison RuchinskasFrederick National Laboratory for Cancer Research, Leidos Biomedical Research, Inc., Frederick, MD 20701, USA.
Kimia DadkhahFrederick National Laboratory for Cancer Research, Leidos Biomedical Research, Inc., Frederick, MD 20701, USA.
Whitney DoLaboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA.
Shay BehrensLaboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA; Surgical Oncology Program, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA.
Farid R MehrabadiLaboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA.
Dana A DominguezLaboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA; Department of Surgical Oncology, City of Hope National Medical Center, Duarte, CA 91010, USA.
Marshonna ForguesLaboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA.
Anuradha BudhuLiver Cancer Program, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA.
Jittiporn ChaisaingmongkolLaboratory of Chemical Carcinogenesis, Chulabhorn Research Institute, Bangkok 10210, Thailand; Center of Excellence on Environmental Health and Toxicology, Office of Higher Education Commission, Ministry of Higher Education, Science, Research and Innovation, Bangkok 10400, Thailand.
Jonathan M HernandezLiver Cancer Program, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA; Surgical Oncology Program, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA.
Jeremy L DavisSurgical Oncology Program, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA.
Bao TranFrederick National Laboratory for Cancer Research, Leidos Biomedical Research, Inc., Frederick, MD 20701, USA.
Jens U MarquardtDepartment of Medicine I, University of Lübeck, 23552 Lübeck, Germany.
Mathuros RuchirawatLaboratory of Chemical Carcinogenesis, Chulabhorn Research Institute, Bangkok 10210, Thailand; Center of Excellence on Environmental Health and Toxicology, Office of Higher Education Commission, Ministry of Higher Education, Science, Research and Innovation, Bangkok 10400, Thailand.
Michael KellyFrederick National Laboratory for Cancer Research, Leidos Biomedical Research, Inc., Frederick, MD 20701, USA.
Tim F GretenLiver Cancer Program, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA; Thoracic and GI Malignancies Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA.
Xin W WangLaboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA; Liver Cancer Program, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA. Electronic address: xw3u@nih.gov.
National Cancer Institute · USLeidos (United States) · USChulabhorn Research Institute · THCity Of Hope National Medical Center · USMedizinische Hochschule Hannover · DEUniversity of Lübeck · DE
Funding
WORK ORDER 126643 B539 EXPAND IC SUITE75N91019D00024 · NIAID · LEIDOS BIOMEDICAL RESEARCH, INC. · PI BRISCOE, LYNN · 2019 to 2025
$3932.6MStrategies for improving early detection, diagnosis and treatment of liver cancerZIABC010313 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI WANG, XIN WEI · 2009 to 2025
$18.1MThe role of cancer stem cells in liver cancer heterogeneity and subtypesZIABC010876 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI WANG, XIN WEI · 2009 to 2025
$12.6MLiver Cancer ProgramZIABC011870 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI WANG, XIN WEI · 2019 to 2025
$10.1MThe identification of human hepatocellular carcinoma metastasis genesZIABC010877 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI WANG, XIN WEI · 2009 to 2025
$8.3MMolecular signatures for liver cancer diagnosis and treatment stratificationZ01BC010313 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI WANG, XIN WEI · 1999 to 2008
$1.8MThe role of cancer stem cells in liver cancer heterogeneity and subtypesZ01BC010876 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI WANG, XIN · 2008 to 2008
$490kThe identification of human hepatocellular carcinoma metastasis genesZ01BC010877 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI WANG, XIN · 2008 to 2008
$327kIntramural NIH HHS Z01 BC010313Intramural NIH HHS Z01 BC010876Intramural NIH HHS Z01 BC010877Intramural NIH HHS ZIA BC010313Intramural NIH HHS ZIA BC010876Intramural NIH HHS ZIA BC010877Intramural NIH HHS ZIA BC011870NCI NIH HHS 75N91019D00024
Abstract
Primary liver cancer (PLC) consists of two main histological subtypes; hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (iCCA). The role of transcription factors (TFs) in malignant hepatobiliary lineage commitment between HCC and iCCA remains underexplored. Here, we present genome-wide profiling of transcription regulatory elements of 16 PLC patients using single-cell assay for transposase accessible chromatin sequencing. Single-cell open chromatin profiles reflect the compositional diversity of liver cancer, identifying both malignant and microenvironment component cells. TF motif enrichment levels of 31 TFs strongly discriminate HCC from iCCA tumors. These TFs are members of the nuclear/retinoid receptor, POU, or ETS motif families. POU factors are associated with prognostic features in iCCA. Overall, nuclear receptors, ETS and POU TF motif families delineate transcription regulation between HCC and iCCA tumors, which may be relevant to development and selection of PLC subtype-specific therapeutics.
Indexed as
Bile Duct NeoplasmsCarcinoma, HepatocellularCholangiocarcinomaLiver NeoplasmsBile Ducts, IntrahepaticChromatinHumansTranscription FactorsTumor MicroenvironmentChromatinTranscription FactorsCP: CancerETShepatocellular carcinomaintrahepatic cholangiocarcinomanuclear receptorsPOUprimary liver cancerretinoid receptorsscATAC-seqtranscription factor
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