Similar Datasets
Project description:Epigenetic consequences of DMSO treatment on the HepaRG cell line
| PRJNA746146 | ENA
Project description:Gene expression profile analysis allowed to identify a panel of genes characteristic of HepaRG differentiation and DMSO effect on the differentiation process.
2022-09-06 | GSE112123 | GEO
Project description:Dimethyl sulfoxide (DMSO) is used to sustain or favor hepatocyte differentiation in vitro. Thus, DMSO is used in the differentiation protocol of the HepaRG cells that present the closest drug-metabolizing enzyme activities to primary human hepatocytes in culture. The aim of our study is to clarify its influence on liver-specific gene expression. For that purpose, we performed a large-scale analysis (gene expression and histone modification) to determine the global role of DMSO exposure during the differentiation process of the HepaRG cells. The addition of DMSO drives the upregulation of genes mainly regulated by PXR and PPARα whereas genes not affected by this addition are regulated by HNF1α, HNF4α, and PPARα. DMSO-differentiated-HepaRG cells show a differential expression for genes regulated by histone acetylation, while differentiated-HepaRG cells without DMSO show gene signatures associated with histone deacetylases. In addition, we observed an interplay between cytoskeleton organization and EMC remodeling with hepatocyte maturation.
| S-EPMC9331440 | biostudies-literature
Project description:Comparison of expression profiles detected inundifferemtitated HepaRG cells exposed to DMSO, TCDD for 24h. The aryl hydrocarbon receptor (AhR) activation has been shown to stimulate proliferation, promote apoptosis or alter differentiation of adult rat liver progenitors. We investigated the impact of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-mediated AhR activation on a human model of bipotent liver progenitors, undifferentiated HepaRG cells. We used both intact undifferentiated HepaRG cells, and HepaRG cells with silenced Hippo pathway effectors, YAP1 and TAZ, which play key role(s) in tissue specific progenitor cell self-renewal and expansion, including liver, cardiac or respiratory progenitors.
2019-09-01 | GSE122518 | GEO
Project description:Primary hepatocytes are widely utilized for investigating drug efficacy and toxicity, yet variations between batches and limited proliferation capacity present significant challenges. HepaRG cells are versatile cells, capable of maintaining an undifferentiated state and differentiating through dimethyl sulfoxide treatment, allowing for molecular analysis of hepatocyte plasticity. To elucidate the underlying molecular mechanisms of HepaRG cell plasticity, we used CYP3A4G/7R HepaRG cells engineered to express DsRed under the control of the fetus-specific CYP3A7 gene and EGFP under the adult-specific CYP3A4 gene promoter. In time-lapse imaging of CYP3A4G/7R HepaRG cells, we observed CYP3A7-DsRed expression transitioning from negative to positive during proliferation period and CYP3A4-GFP expression activating during differentiation. The de-differentiation potency of differentiated CYP3A4G/7R HepaRG cells was assessed using inhibitors and cytokines. It was found that Y-27632 (Y), A-83-01 (A), and CHIR99021 (C) (collectively referred to as YAC), which are known to promote liver regeneration in mice, did not induce CYP3A7-DsRed expression. Instead, these inhibitors increased CYP3A4-GFP expressing population. Furthermore, CHIR99021 alone increased CYP3A4-GFP-positive cells, while Wnt3a treatment increased CYP3A7-DsRed-positive cells, suggesting that Wnt signaling plays distinct roles in HepaRG cells. It was apparent that de-differentiated cells had increased CYP3A4 activity after a second round of differentiation, compared to differentiated cells after the first round. Transcriptomic analysis of HepaRG cells revealed distinct profiles between proliferative, differentiated, and de-differentiated states, highlighting their robust plasticity. Notably, hepatoblastic cells de-differentiated by YAC or C displayed transcriptome patterns similar to undifferentiated cells, whereas CYP3A7-DsRed and CYP3A4-GFP exhibited expression patterns different from those of undifferentiated cells. These findings underscore the dynamic nature of HepaRG cells while cautioning against solely relying on CYP3 family gene expression as a marker of differentiation.
2024-09-18 | GSE272892 | GEO
Project description:Gene expression profile analysis allowed to identify a panel of genes and pathways characteristic of hESC-and HepaRG-derived cholangiocytes. Microarrays were conducted at day 23 and day 10 of differentiation for hESC-Chol and HepaRG-Chol respectively and compared to hESC-HB and HepaRG-HB. Five, four or three independent experiments were performed depending the experimental sample
2013-10-28 | E-GEOD-51791 | biostudies-arrayexpress
Project description:The aim of the study was to characterize at a molecular level (changes in mRNA level) the effects of WNT3A on the human HepaRG hepatocellular carcinoma cell line. This was adressed by culturing HepaRG cells in presence or absence of Wnt3a.
2017-02-11 | GSE68633 | GEO
Project description:HepaRG cell, a stabilized bipotent liver progenitor cell line, exhibits hepatocyte functions only after differentiation. However, the mechanism of transition from non-differentiated to differentiated states, accompanied by proliferation and migration, is poorly understood. Little information exists for proteins involved in this process, particularly those residing in the plasma membrane. In this study, the plasma membrane protein expression change of HepaRG cell before and after differentiation were systematically analyzed using an iTRAQ labeled quantitative membrane proteomics approach. A total of 70 membrane proteins were identified to be differentially expressed. Function and disease clustering analysis showed that 11 of these proteins are involved in migration. Two key factors (MMP-14 and OCLN) were validated by qRT-PCR and Western Blot. Blockade of MMP-14, an extracellular matrix metalloprotease, by monoclonal antibody in a wound healing assay further demonstrated the importance of this protein in tumor cell migration. Even further, the MMP-14 expression correlation with HCC is confirmed by HCC cell lines and tissue samples.
2017-02-08 | PXD004752 | Pride
Project description:We used scRNA-seq to characterise the differentiation status of HepaRG cells after applying standard differentiation protocols on these cells. For downstream Perturb-seq we also characterised two cell lines of different genotype; Wt and cells transduced with dCas9-KRAB.
2024-08-29 | GSE261025 | GEO
Project description:The exposure to and contamination by Persistent Organic Pollutants (POPs), which include pesticides used worldwide and polyaromatic hydrocarbons, is detrimental to human health and diverse ecosystems. Although most mechanistic studies have focused on single compounds, living organisms are exposed to multiple environmental xenobiotics, simultaneously, throughout their lives. The experimental evidence useful for assessing the effects of exposure to pollutant mixtures is scarce. We investigated the effects of exposure to a combination of two POPs, which employ different xenosensors, on global gene expression in a human hepatocyte cell model, HepaRG. Whole genome microarrays were used to investigate the effects on the HepaRG transcriptome following exposure to the combination of POPs as compared to each compound individually. Differentiated HepaRG cells were treated with either 2,3,7,8 tetrachlorodibenzo-p-dioxin, alpha-endosulfan (an organochlorine pesticide), the mixture or the DMSO vehicle for 30 hours after which RNA was extracted for hybridization on Affymetrix whole human genome microarrays.
2016-07-03 | E-GEOD-46874 | biostudies-arrayexpress