Hepatocytes :MH vs. ProliHH vs. PHH vs. HLC
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE192653 | GEO | 2021/12/30
REPOSITORIES: GEO
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Project description:Hepatocytes :MH vs. ProliHH vs. PHH vs. HLC
| PRJNA792566 | ENA
Project description:Drug induced liver injury (DILI) is still a major reason for drug attrition during clinical trials and market-withdrawal of already approved drugs. DILI is difficult to predict in animal models, hence more suitable screening methods are needed to predict adverse effects in human. Here, transcriptomic data from short- and long-term cultured primary human hepatocytes exposed to the human hepatotoxin Chlorpromazine was analysed.
2013-08-05 | E-MTAB-1747 | biostudies-arrayexpress
Project description:The differentiation of pluripotent stem cells to hepatocyte-like cells offers the perspective of unlimited supply of human hepatocytes. However, the degree of differentiation of hepatic-like cells (HLC) remains controversial. To obtain an unbiased characterization, we performed a transcriptomics study using the Affymetrix Gene Chip® HG-U133 plus 2.0, with HLC derived from embryonic and induced stem cells (ESC, hiPSC) from two different laboratories. Genome-wide gene expression profiles of ESC and HLC were compared to freshly isolated and up to 14 days cultivated primary human hepatocytes (see submission E-MTAB-3994) obtained under patient informed consent from three male donors. Three biological replicas were used for each ESC and HLC models. (associated data set: E-MTAB-3994 - Gene expression profile of human embryonic stem cell-derived hepatocyte-like cells in matrigel and recombinant laminins)
2016-02-24 | E-MTAB-4442 | biostudies-arrayexpress
Project description:Interindividual differences in hepatic metabolism, which are mainly due to genetic polymorphism in its gene, have a large influence on individual drug efficacy and adverse reaction. Hepatocyte-like cells (HLCs) differentiated from human induced pluripotent stem (iPS) cells have the potential to predict interindividual differences in drug metabolism capacity and drug response. However, it remains uncertain whether human iPSC-derived HLCs can reproduce the interindividual difference in hepatic metabolism and drug response. We found that cytochrome P450 (CYP) metabolism capacity and drug responsiveness of the primary human hepatocytes (PHH)-iPSHLCs were highly correlated with those of PHHs, suggesting that the PHH-iPS-HLCs retained donor-specific CYP metabolism capacity and drug responsiveness. We also demonstrated that the interindividual differences, which are due to the diversity of individual SNPs in the CYP gene, could also be reproduced in PHH-iPS-HLCs. We succeeded in establishing, to our knowledge, the first PHH-iPS-HLC panel that reflects the interindividual differences of hepatic drugmetabolizing capacity and drug responsiveness.
2014-11-12 | GSE61287 | GEO
Project description:Robust and scalable differentiation of human pluripotent stem cells into high-quality hepatocyte-like cells (HLC) is achieved by acting on Wnt/b-catenin and TGFb pathways and taking advantage of latest knowledge on human liver development. Obtained HLC are comparable to primary human hepatocytes and superior to stem cell-derived hepatocytes generated with previously described protocols. As a proof of concept, such HLC were used to assess drug hepatotoxicity and study human ductal plate and bile duct morphogenesis in a complex liver organoid model.
2022-02-03 | GSE152390 | GEO
Project description:Recent advances towards the efficient and reproducible differentiation of stem cells into hepatocyte-like cells (HLC) have created potential opportunities in clinical transplantation. For this approach to be successfully translated, however, it is necessary to understand the immune response to stem cell-derived cellular products. Whereas both embryonic stem cells and induced pluripotent stem cells have been utilized as cellular sources for differentiation and lineage specification, their relative ability to be recognized by immune effector cells is unclear. Here we determine the expression of immune recognition molecules on HLC generated from murine embryonic stem cells and induced pluripotent stem cells, compared to adult hepatocytes, and we evaluate the impact on recognition by NK cells. We report that HLC lack MHC class I expression, and that embryonic stem cell derived-HLC have higher expression of the NK cell activating ligands Rae1, H60, and Mult1 than induced pluripotent stem cell-derived HLC and adult hepatocytes. Moreover, the lack of MHC class I render embryonic stem cell derived-HLC, and induced pluripotent stem cell derived-HLC, susceptible to killing by syngeneic and allogeneic NK cells. Both embryonic stem cell derived-HLC, and induced pluripotent stem cell derived-HLC, are killed by NK cells at higher levels than adult hepatocytes. Finally, we demonstrate that the NK cell activation receptor, NKG2D, plays a key role in NK cell killing of embryonic stem cell derived-HLC, but not induced pluripotent stem cell-derived HLC. Hepatocytes were isolated from FVB/NJ mice and C57Bl/6 mice using a modification of the Seglen’s perfusion technique.
2017-11-14 | GSE106829 | GEO
Project description:Idiosyncratic drug-induced liver injury (DILI) is a rare, often difficult to predict adverse reaction with complex pathomechanisms. However, it is now evident that certain forms of DILI are immune-mediated and may involve the activation of drug-specific T-cells. Exosomes are cell-derived vesicles that carry RNA, lipids and protein cargo from their cell of origin to distant cells, and may play a role in immune activation. Herein, primary human hepatocytes were treated with drugs associated with a high incidence of DILI (flucloxacillin, amoxicillin, isoniazid and nitroso-sulfamethoxazole) to characterize the proteins packaged within exosomes that are subsequently transported to dendritic cells for processing. Exosomes measured between 50-100 nm and expressed CD63. LC-MS/MS identified an average of 1200 proteins across all exosome samples. Analysis of gene ontologies revealed that exosomes mirrored whole human liver tissue in terms of the families of proteins present, regardless of drug treatment. However, exosomes from nitroso-sulfamethoxazole-treated hepatocytes selectively packaged a specific subset of proteins. LC-MS also revealed the presence of hepatocyte-derived exosomal proteins covalently modified with amoxicillin, flucloxacillin and nitroso-sulfamethoxazole. Uptake of exosomes by monocyte-derived dendritic cells occurred mainly via phagocytosis, and was inhibited by latrunculin A. This study reveals that exosomes have the potential to transmit drug-specific hepatocyte-derived signals to the immune system and provides a pathway for the induction of drug hapten-specific T-cell responses.
2019-05-14 | PXD010760 | Pride
Project description:Human pluripotent stem cells (hPSCs) can differentiate into all cell types in the body that may replace current cell sources applied in regenerative medicine, cell therapy, drug discovery and development and general research. Human PSC-derived hepatocyte-like cells (HLCs) have the potential to replace primary hepatocytes and other cell models applied in liver disease treatment and drug discovery and development. These cells share many features with their in vivo counterparts however, the generation of fully functional hPSC-derive HLCs is still lacking, which prevent their application in the previously mentioned fields. This study followed the transcriptome dynamics during the differentiation of hPSC-derived HLCs at definitive endoderm, hepatoblast, early HLC and late HLC developmental stages and the controls hPSCs and human liver tissues which consists of at least 70% hepatocytes. The aim is to reveal expression deviations between hPSC-derived hepatocytes and their in vivo counterparts that may contribute to the modification of differentiation protocols to generate fully functional hepatocytes.
2017-08-09 | E-MTAB-5367 | biostudies-arrayexpress
Project description:During embryonic development bipotential hepatoblasts differentiate into hepatocytes and cholangiocytes- the two main cell types within the liver. Cell fate decision depends on elaborate interactions between distinct signalling pathways, namely Notch, WNT, TGFβ, and Hedgehog. Several in vitro protocols have been established to differentiate human pluripotent stem cells into either hepatocyte or cholangiocyte like cells (HLC/CLC) to enable disease modelling or drug screening. During HLC differentiation we observed the occurrence of epithelial cells with a phenotype divergent from the typical hepatic polygonal shape- we refer to these as endoderm derived epithelial cells (EDECs). These cells do not express the mature hepatocyte marker ALB or the progenitor marker AFP. However they express the cholangiocyte markers SOX9, OPN, CFTR as well as HNF4α, CK18 and CK19. Interestingly, they express both E Cadherin and Vimentin, two markers that are mutually exclusive, except for cancer cells. EDECs grow spontaneously under low density cell culture conditions and their occurrence was unaffected by interfering with the above mentioned signalling pathways.
2018-06-30 | GSE116455 | GEO
Project description:Hepatitis B virus (HBV) is known for its ability to interact with the host cell DNA methylation machinery. In HBV-infected hepatocytes, this interaction leads to chronic liver diseases, including hepatocellular carcinoma (HCC). We studied the extent of genomic changes induced by natural HBV infection in human primary hepatocytes. Transcriptome and methylome profiles were obtained at different time points post-infection to identify HBV-specific alterations. Although gene expression and DNA methylation do not directly correlate, they both seem to reflect the effect of cell culture and viral infection at different levels.These changes in the hepatocyte cellular program shed light on the initial events leading to HBV-associated liver diseases.
2016-01-01 | GSE72068 | GEO