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

ABSTRACT: 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

ORGANISM(S): Homo sapiens

PROVIDER: GSE80279 | GEO | 2016/12/22

SECONDARY ACCESSION(S): PRJNA318486

REPOSITORIES: GEO

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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

Human induced pluripotent stem cell-derived hepatic stellate-like cells (iPS-HSCs) overexpressing LHX2 vs control iPS-HSCs

Project description:Transcriptional profiling of human iPS-HSCs overexpressing LHX2 compared with control iPS-HSCs, which were cocultured with human induced pluripotent stem cell-derived hepatic progenitor cells (iPS-HPCs).

2019-02-14 | GSE122750 | GEO

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

Genome-wide map of binding sites for HNF4a during hepatic specification of iPS cells

Project description:HNF4a has been shown to be critical for hepatocyte differentiation from iPS cells.

2019-01-28 | GSE104613 | GEO

Human patient iPS cell-derived hepatostellate organoids establish a cellular and molecular basis for liver pathologies in telomeropathies

Project description:Patients with dyskeratosis congenita (DC) and related telomeropathies resulting from premature telomere dysfunction suffer from multi-organ failure. In the liver, DC patients present with nodular hyperplasia and cirrhosis. We model DC liver pathologies using isogenic human induced pluripotent stem (iPS) cells harboring a causal DC mutation in DKC1, or a clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9-corrected control allele. Differentiation of these iPS cells into hepatocytes or hepatic stellate cells reveals a dominant phenotype in the parenchyma. Generation of genotype admixed hepatostellate organoids indicates that DC hepatocytes elicit a pathogenic hyperplastic response in stellate cells independent of stellate cell genotype. Phenotypic rescue was achieved via suppression of AKT activity, a central regulator of mTORC1, MYC, and DC hepatocyte-driven hyperplasia. Thus, isogenic, iPS-derived admixed hepatostellate organoids offer insight into the liver pathologies in telomeropathies and provide a framework for evaluating emerging therapies.

2023-05-06 | GSE174018 | GEO

High-throughput sequencing of sequentially reprogrammed iPS cells reveals key epigenetic modifications correlated with reduced pluripotency of iPS cells [sRNA-seq]

Project description:Full pluripotency of induced pluripotent stem (iPS) cells has been determined as viable all-iPS mice can be generated through tetraploid complementation. Subsequently, activation of imprinted Dlk-Dio3 gene cluster has been suggested to correlate with the pluripotency of iPS cells1. However, evidence from recent studies has demonstrated that loss of imprinting at the Dlk-Dio3 locus did not correlate strictly with the reduced pluripotency of iPS cells. Therefore, it becomes indispensable to exploit other reliable molecular markers for evaluating the quality of iPS cells accurately. In the present study, we successfully utilize the sequential reprogramming approach and produce all-iPS mice to six generations using iPS cell lines derived from different cell lineages which contain the same proviral integration in the genome. By comparing the global gene expression and epigenetic modifications of both “tetra-on” and corresponding “tetra-off” iPS cell lines established from either mesenchymal or hematopoietic lineages through deep sequencing analysis of mRNA expression, small RNA profiling, histone modifications (H3K4m2, H3K4me3 and H3K27me3) and DNA methylation, very few differences are detected among all the iPS cell lines investigated. However, we find that two imprinted genes, disruption of which correlate with the reduced pluripotency of iPS cells. Therefore, our data not only provide the first demonstration that producing of all-iPS mice to six generations is feasible, but reveal that two imprinted regions can be served as pluripotency markers of iPS cells

2013-12-06 | GSE36291 | GEO

High-throughput sequencing of sequentially reprogrammed iPS cells reveals key epigenetic modifications correlated with reduced pluripotency of iPS cells [RNA-seq]

Project description:Full pluripotency of induced pluripotent stem (iPS) cells has been determined as viable all-iPS mice can be generated through tetraploid complementation. Subsequently, activation of imprinted Dlk-Dio3 gene cluster has been suggested to correlate with the pluripotency of iPS cells1. However, evidence from recent studies has demonstrated that loss of imprinting at the Dlk-Dio3 locus did not correlate strictly with the reduced pluripotency of iPS cells. Therefore, it becomes indispensable to exploit other reliable molecular markers for evaluating the quality of iPS cells accurately. In the present study, we successfully utilize the sequential reprogramming approach and produce all-iPS mice to six generations using iPS cell lines derived from different cell lineages which contain the same proviral integration in the genome. By comparing the global gene expression and epigenetic modifications of both "tetra-on" and corresponding "tetra-off" iPS cell lines established from either mesenchymal or hematopoietic lineages through deep sequencing analysis of mRNA expression, small RNA profiling, histone modifications (H3K4m2, H3K4me3 and H3K27me3) and DNA methylation, very few differences are detected among all the iPS cell lines investigated. However, we find that two imprinted genes, disruption of which correlate with the reduced pluripotency of iPS cells. Therefore, our data not only provide the first demonstration that producing of all-iPS mice to six generations is feasible, but reveal that two imprinted regions can be served as pluripotency markers of iPS cells.

2013-12-06 | GSE36290 | GEO

High-throughput sequencing of sequentially reprogrammed iPS cells reveals key epigenetic modifications correlated with reduced pluripotency of iPS cells [MeDIP-seq]

2013-12-06 | GSE36293 | GEO

High-throughput sequencing of sequentially reprogrammed iPS cells reveals key epigenetic modifications correlated with reduced pluripotency of iPS cells [ChIP-seq]

2013-12-06 | GSE36292 | GEO

Expression of genes in hepatic progenitor-like cells derived from human iPS cells

Project description:To analyze stem/progenitor cell function, we purified hepatic progenitor-like cells in human iPS cell culture stimulated with cytokines.

2015-03-04 | GSE66450 | GEO

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