ArticleOncotarget2015
Genome-wide analysis of DNA methylation and gene expression patterns in purified, uncultured human liver cells and activated hepatic stellate cells.
Article in Oncotarget, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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Who cites it
38 citing papers in PubMed, 81 citations in OpenAlex.
- Liver sinusoidal endothelial cells in liver diseases and hepatocellular carcinoma: molecular mechanisms, physiology, and therapies.Molecular biomedicine · 2026Review
- Article
- Genomic identification of recipient-derived hepatocytes in liver transplantation: a hypothesis linking graft repopulation to immune tolerance.Frontiers in immunology · 2025Review
- The role of pioneering transcription factors, chromatin accessibility and epigenetic reprogramming in oncogenic viruses.Frontiers in microbiology · 2025Review
- Conditional deletion of CEACAM1 in hepatic stellate cells causes their activation.Molecular metabolism · 2024Article
- Liver Fibrosis: From Basic Science towards Clinical Progress, Focusing on the Central Role of Hepatic Stellate Cells.International journal of molecular sciences · 2024Review
- O-GlcNAcylation controls pro-fibrotic transcriptional regulatory signaling in myofibroblasts.Cell death & disease · 2024Article
- Endothelial gene regulatory elements associated with cardiopharyngeal lineage differentiation.Communications biology · 2024Article
- Genome-wide CRISPR Screening to Identify Drivers of TGF-β-Induced Liver Fibrosis in Human Hepatic Stellate Cells.ACS chemical biology · 2022Article
- Single-cell transcriptomic analysis reveals a novel cell state and switching genes during hepatic stellate cell activation in vitro.Journal of translational medicine · 2022Article
- Glia Maturation Factor-β Supports Liver Regeneration by Remodeling Actin Network to Enhance STAT3 Proliferative Signals.Cellular and molecular gastroenterology and hepatology · 2022Article
- Development of human iPSC-derived quiescent hepatic stellate cell-like cells for drug discovery and in vitro disease modeling.Stem cell reports · 2021Article
- Review
- Single-cell RNA sequencing of human liver reveals hepatic stellate cell heterogeneity.JHEP reports : innovation in hepatology · 2021Article
- The roles and mechanisms of hypoxia in liver fibrosis.Journal of translational medicine · 2021Review
- Hepatic Stellate Cell Activation and Inactivation in NASH-Fibrosis-Roles as Putative Treatment Targets?Biomedicines · 2021Review
- Role of long non‑coding RNAs and related epigenetic mechanisms in liver fibrosis (Review).International journal of molecular medicine · 2021Review
- Article
- DNA Methylation in Nonalcoholic Fatty Liver Disease.International journal of molecular sciences · 2020Review
- Molecular Analysis of Fetal and Adult Primary Human Liver Sinusoidal Endothelial Cells: A Comparison to Other Endothelial Cells.International journal of molecular sciences · 2020Article
Corrections and comments
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Authors and funding
14 authors at 6 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
BACKGROUND &
aimsLiver fibrogenesis - scarring of the liver that can lead to cirrhosis and liver cancer - is characterized by hepatocyte impairment, capillarization of liver sinusoidal endothelial cells (LSECs) and hepatic stellate cell (HSC) activation. To date, the molecular determinants of a healthy human liver cell phenotype remain largely uncharacterized. Here, we assess the transcriptome and the genome-wide promoter methylome specific for purified, non-cultured human hepatocytes, LSECs and HSCs, and investigate the nature of epigenetic changes accompanying transcriptional changes associated with activation of HSCs. MATERIAL AND
methodsGene expression profile and promoter methylome of purified, uncultured human liver cells and culture-activated HSCs were respectively determined using Affymetrix HG-U219 genechips and by methylated DNA immunoprecipitation coupled to promoter array hybridization. Histone modification patterns were assessed at the single-gene level by chromatin immunoprecipitation and quantitative PCR.
resultsWe unveil a DNA-methylation-based epigenetic relationship between hepatocytes, LSECs and HSCs despite their distinct ontogeny. We show that liver cell type-specific DNA methylation targets early developmental and differentiation-associated functions. Integrative analysis of promoter methylome and transcriptome reveals partial concordance between DNA methylation and transcriptional changes associated with human HSC activation. Further, we identify concordant histone methylation and acetylation changes in the promoter and putative novel enhancer elements of genes involved in liver fibrosis.
conclusionsOur study provides the first epigenetic blueprint of three distinct freshly isolated, human hepatic cell types and of epigenetic changes elicited upon HSC activation.
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