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Gene expression profiles in CYP2C19-deficient human iPS cell-derived hepatocyte-like cells

ABSTRACT: Gene expression profiles in CYP2C19-deficient human iPS cell-derived hepatocyte-like cells

PROVIDER: PRJNA510356 | ENA |

REPOSITORIES: ENA

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Gene expression profiles in CYP2C19-deficient human iPS cell-derived hepatocyte-like cells

Project description:Cytochrome P450 family 2 subfamily C member 19 (CYP2C19), in liver, plays important roles in terms of drug metabolism. It is known that CYP2C19 poor metabolizers (PMs) lack CYP2C19 metabolic capacity. Thus, unexpected drug-induced liver injury or decrease of drug efficacy would be caused in CYP2C19 substrate-treated CYP2C19 PMs. However, it is difficult to evaluate the safety and effectiveness of drugs and candidate compounds for CYP2C19 PMs because there is currently no model for this phenotype. Here, using human iPS cells and our highly efficient genome editing and hepatocyte differentiation technologies, we generated CYP2C19-knockout human iPS cell-derived hepatocyte-like cells (CYP2C19-KO HLCs) as a novel CYP2C19 PM model for drug development and research. The gene expression levels of hepatocyte markers were similar between WT HLCs and CYP2C19-KO HLCs, suggesting that CYP2C19 deficiency did not affect the hepatic differentiation potency. We also examined CYP2C19 metabolic activity by measuring S-mephenytoin metabolites using LC-MS. The CYP2C19 metabolic activity was almost eliminated by CYP2C19 knockout. Additionally, we evaluated whether clopidogrel (CYP2C19 substrate)-induced liver toxicity could be predicted using our model. Unexpectedly, there was no significant difference in cell viability between clopidogrel-treated WT HLCs and CYP2C19-KO HLCs. However, the cell viability in clopidogrel- and ketoconazole (CYP3A4 inhibitor)-treated CYP2C19-KO HLCs was significantly enhanced as compared with that in clopidogrel- and DMSO-treated CYP2C19-KO HLCs. This result suggests that CYP2C19-KO HLCs can predict the clopidogrel-induced liver toxicity. We succeeded in generating CYP2C19 PM model cells using human iPS cells and genome editing technologies for pharmaceutical research.

2019-05-07 | GSE123937 | GEO

Gene expression profiles in SOX10-deficient human iPS cell-derived neural crest cells

Project description:Gene expression profiles in SOX10-deficient human iPS cell-derived neural crest cells

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Expression data from iPS cell derived hepatocyte-like cells sorted with antibody against cell surface protein SLC10A1

Project description:Most differentiation protocols for generation of hepatocyte-like cells from iPS cells generate cells with heterogenous expression of hepatic markers, which confounds results from liver disease models involving complex traits and subtle phenotypes We utilized proteomics to identify heptocyte-restricted cell surface proteins that mark a subpopulation of iPS cell derived hepatocytes. By performing microarray on FACS sorted cells, we demonstrate that subpopulation of hepatocyte-like cells expressing SLC10A1 are enriched for hepatic markers

2016-12-22 | GSE80279 | GEO

Expression data from control and Smith-Lemli-Opitz syndrome patient-derived iPS cells - comparison of cholesterol deficient and cholesterol rich culture

Project description:7-dehydrocholesterol reductase catalyzes the reduction of 7-dehydrocholesterol to cholesterol. In Smith-Lemli-Opitz syndrome, mutations in DHCR7 prevents this conversion. We have found iPS cells derived from SLOS patients exhibit accelerated differentiation under cholesterol poor conditions. In this dataset, we include expression data obtained from comparision of a control iPS cell line (BJ) and a SLOS iPS cell line (A2). Cell line gene expression was compared in cholesterol rich conditions where the SLOS phenotype is suppressed. Cholesterol deficient culture of control and SLOS iPS cells demonstrated enhanced differentiation of SLOS cells over 7 days. These data are used to obtain 308 genes that are differentially expressed upon cholesterol deficient culture. time-course expression data obtained from control and SLOS patient iPS cells after transfer from cholesterol rich to cholesterol deficient culture.

2015-09-18 | GSE61203 | GEO

Gene expression profiles in human iPS cells cultured by different four methods

Project description:Hepatocyte-like cells differentiated from human iPS cells are expected to be utilized in pharmaceutical research and regenerative medicine. Recently, various culture methods for human iPS cell maintenance have been developed. However, it is not well known whether human iPS cell maintenance method affects hepatic differentiation potency. In this study, we cultured human iPS cells using four maintenance methods: ReproStem medium with feeder cells (mouse embryonic fibroblasts), AK02N medium with iMatrix-511 (E8 fragments of laminin511), Essential 8 medium with Vitronectin N (N-terminal domain of vitronectin), TeSR-E8 medium with Vitronectin XF (xeno-free vitronectin). Then, these human iPS cells were differentiated into the hepatocyte-like cells. Interestingly, the gene expression levels of definitive endoderm markers in the definitive endoderm cells generated from human iPS cells cultured with ReproStem or TeSR-E8 medium were higher than those in other groups. The gene expression level of foregut marker, HHEX, in the definitive endoderm cells generated from human iPS cells cultured with ReproStem medium was higher than that in other groups. Consistently, the expression levels of hepatocyte markers, albumin and urea secretion capacity, and CYP3A4 activity in the hepatocyte-like cells generated from human iPS cells cultured with ReproStem medium were higher than those in other groups. Our data indicated that the most suitable human iPS cell maintenance method for efficient hepatic differentiation was the on-feeder method which uses mouse embryonic fibroblasts, but not feeder-free methods. In conclusion, human iPS cell maintenance method largely affects hepatic differentiation potency.

2018-09-25 | GSE119698 | GEO

iPS derived melanocyte precursor cells

Project description:iPS derived melanocyte precursor cells

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Comparison of the gene expression profiles between iPS-OSH, iPS-J, ESC and MEF.

Project description:iPS-OSH was the novel iPS cells generated from our lab, the microarray analysis was used for determining the gene expression profiles of iPS-OSH. iPS-J was provided from Dr. Yamanaka (Riken, APS0001). Microarray analysis was used to compare the difference of gene expression profiles in iPS-OSH, iPS-J, ESC and MEF.

2012-08-01 | GSE31822 | GEO

Gene expression profiles of hepatocyte-like cells derived from induced pluripotent stem cells (iPSCs) from donors with the Zellweger spectrum of peroxisome biogenesis disorders (PBD-ZSD) and healthy controls

Project description:Skin fibroblasts from individuals with PBD-ZSD, a rare autosomal recessive disorder caused by peroxisome assembly defects, show defects in lipid metabolism that provide the basis for clinical diagnostic tests, but are not among the cell types most affected by disease. To explore phenotypes of more clinically relevant cell types, skin fibroblasts from PBD-ZSD patients and healthy controls were reprogrammed into iPS cells with all the hallmark properties of pluripotency. Subsequently, iPSCs were differentiated into ASGPR-positive hepatocyte-like cells that were subject to flow cytometry and subject to gene expression profiling. We report the gene expression profiles of hepatocyte-like cells derived from iPSCs that were themselves derived from skin fibroblasts from PBD-ZSD patient donors and healthy controls.

2015-05-21 | GSE69066 | GEO

PKHD1-deficient human induced pluripotent stem (iPS) cell-derived cholangiocyte-like cells (PKHD1-KO CCs) vs heterozygously mutated PKHD1 human iPS cell-derived cholangiocyte-like cells (PKHD1-Hetero CCs)

Project description:Transcriptional profiling of PKHD1-KO and PKHD1-Hetero CCs. PKHD1-deficient (PKHD1-KO) and heterozygously mutated PKHD1 iPS clones were established by RNA-guided genome editing using CRISPR/Cas9 system. The iPS clones were differentiated into cholangiocyte-like cells in cysts (cholangiocytic cysts, CCs) in a 3D-culture system.

2019-03-19 | GSE125871 | GEO

RNA-seq analysis with MFN2-deficient human iPS cells

Project description:We performed Next-generation sequencing analyses with control or MFN2-deficient human iPS cells.

2023-04-01 | GSE226330 | GEO