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DNA methylation profiles of 24 whole cord blood samples from healthy children born via caesarian section with matched FACS counts

ABSTRACT: In order to accurately evaluate methods for dealing with inter-individual differences in cord blood cell type in DNA methylation data, matched samples with both DNAm profiles and detailed FACS counts are necessary.

ORGANISM(S): Homo sapiens

PROVIDER: GSE127824 | GEO | 2019/03/05

REPOSITORIES: GEO

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DNA methylation profiles of 24 whole cord blood samples from healthy children born via caesarian section with matched FACS counts

Project description:DNA methylation profiles of 24 whole cord blood samples from healthy children born via caesarian section with matched FACS counts

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Project description:Background: Asthma is highly heterogeneous and severity evaluation is key to asthma management. DNA methylation (DNAm) contributes to asthma pathogenesis. This study aimed to identify nasal epithelial DNAm differences between severe and non-severe asthmatic children and evaluate the impact of environmental exposures. Methods: Thirty-three non-severe and 22 severe asthmatic African-American children were included in an epigenome-wide association study. Genome-wide nasal epithelial DNAm and gene expression were measured. CpG sites associated with asthma severity and environmental exposures and predictive of severe asthma were identified. DNAm was correlated with gene expression. Enrichment for transcription factor (TF) binding sites or histone modifications surrounding DNAm differences were determined. Results: We identified 816 differentially methylated CpG positions (DMPs) and 10 differentially methylated regions (DMRs) associated with asthma severity. Three DMPs exhibited discriminatory ability for severe asthma. Intriguingly, six DMPs were simultaneously associated with asthma, allergic asthma, total IgE, environmental IgE, and FeNO in an independent cohort of children. 27 DMPs were associated with traffic-related air pollution or secondhand smoke. DNAm at 22 DMPs were altered by diesel particles or allergen in human bronchial epithelial cells. DNAm levels at 39 DMPs were correlated with mRNA expression. Proximal to 816 DMPs, three histone marks and several TFs involved in asthma pathogenesis were enriched. Conclusions: Significant differences in nasal epithelial DNAm were observed between non-severe and severe asthma in African-American children, a subset of which may be useful to predict disease severity. These CpG sites are subject to the influences of environmental exposures and may regulate gene expression.

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Impact of red blood cells on genome-wide DNA methylation and expression analyses of cord blood hematopoietic cells

Project description:Genome-wide DNA methylation (DNAm) studies have been extremely useful to understand hematopoiesis in humans. For cell-specific epigenetic studies, fluorescence-activated cell sorting (FACS) is the gold standard technique to isolate homogeneous cell populations of interest. However, in cord blood, the DNAm signature of isolated hematopoietic cells may be significantly altered by heterotopic interactions with nucleated red blood cells (nRBCs) that go undetected during conventional cell sorting. Using the Illumina 450K array, genome-wide DNAm profiles of the following cell types were obtained: (1) T lymphocytes, monocytes, and nRBCs isolated using a “standard” strategy lacking exclusion for erythroid lineage markers; and (2) CD4 and CD8 T lymphocytes, B lymphocytes, Natural Killer (NK) cells, granulocytes, monocytes, and nRBCs isolated using a “stringent” strategy formally excluding erythroid lineage-specific markers. DNAm profiles of cord blood cells isolated by the standard sorting strategy showed significant heterotopic cross-contamination between cell populations, whereas the cord blood cells sorted by the stringent strategy displayed DNAm profiles more consistent with their expected hematopoietic lineage relationships.

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