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Expression data of human somatic cell types and induced pluripotent stem cells

ABSTRACT: Transcription factor-mediated reprogramming yields induced pluripotent stem cells (iPSC) by erasing tissue specific methylation and re-setting DNA methylation status to an embryonic stage. We compared bona fide human iPSC derived from umbilical cord blood (CB) and neonatal keratinocytes (K). Through both incomplete erasure of tissue specific methylation and de novo tissue specific methylation, CB-iPSC and K-iPSC are distinct in genome-wide DNA methylation profiles. Functionally, CB-iPSC displayed better blood formation in vitro, whereas K-iPSC differentiated better to a keratinocyte fate, implying that the tissue of origin needs to be considered in future therapeutic applications of human iPSCs. We performed gene expression and global DNA methylation profiling on iPS and the source somatic cell types to search for evidence of epigenetic memory.

ORGANISM(S): Homo sapiens

PROVIDER: GSE27186 | GEO | 2011/11/29

SECONDARY ACCESSION(S): PRJNA142053

REPOSITORIES: GEO

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Project description:Genome wide DNA methylation profiling of cord blood in Faroe Island cohort. The Illumina Infinium 450k Human DNA methylation Beadchip was used to obtain DNA methylation profiles across approximately 485,000 CpGs in cord blood samples. Background: Faroe islanders consume marine foods contaminated with methylmercury (MeHg), polychlorinated biphenyls (PCBs), and other toxicants associated with chronic disease risks. Differential DNA methylation at specific CpG sites in cord blood may serve as a surrogate biomarker of health impacts from chemical exposures. Objective: We aimed to identify key environmental chemicals in cord blood associated with DNA methylation changes in a population with elevated exposure to chemical mixtures. Method: We studied 72 participants of a Faroese birth cohort recruited between 1986 and 1987 and followed until adulthood. The cord blood DNA methylome was profiled using Infinium Methylation 450K BeadChips. We determined the associations of CpG site changes with concentrations of MeHg, major PCBs, other organochlorine compounds, (hexachlorobenzene [HCB], p,p’-dichlorodiphenyldichloroethylene [p,p’-DDE] and p,p’-dichlorodiphenyltrichloroethane) and perfluoroalkyl substances. Results: In a combined sex analysis, among the 16 chemicals studied, PCB congener 105 (CB-105) exposure was associated with the majority of differentially methylated CpG sites (214 out of a total of 250). In female-only-analysis, only 73 CB-105 associated CpG sites were detected, 44 of which were mapped to genes in the ELAV1-associated cancer network. In males-only, methylation changes were seen for perfluorooctane sulfonate, HCB, and p,p’-DDE in 10,598; 1,238; and 1,473 CpG sites, respectively, 15% of which were enriched in cytobands of the X chromosome associated with neurological disorders. Conclusion: In this multiple-pollutant and genome-wide study, we identified key epigenetic toxicants. The significant enrichment of specific X-chromosome sites in males implies potentially sex-specific epigenome responses to prenatal chemical exposures.

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Expression data of human somatic cell types and induced pluripotent stem cells

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