Characterizing the Hypomethylated DNA Methylation Profile of Nucleated Red Blood Cells from Cord Blood

Abstract

Aim: To provide insight into fetal nucleated red blood cell (nRBC) development using genome-wide DNA methylation (DNAm) profiling. Materials & methods: The DNAm profile (Illumina 450K array) of cord blood (n = 7) derived nRBCs was compared with B cells, CD4 and CD8 T cells, natural killer cells, granulocytes, monocytes and placenta (n = 5). Results: nRBCs and placenta had similarly low array-wide DNAm compared with white blood cells, but their patterns of hypomethylation differed at biologically relevant subsets of the array. High interindividual variability in nRBC DNAm was driven by a negative association between DNAm and nRBC count. Conclusion: nRBC hypomethylation is likely an epigenetic signature of erythropoiesis rather than of early development. Variability in nRBC DNAm may stem from differences in the cell population’s maturity or hematopoietic source.

Keywords::

• cord blood
• DNA methylation
• epigenetics
• Illumina 450K array
• nucleated red blood cells
• placenta

Supplementary data

To view the supplementary data that accompany this paper please visit the journal website at: www.tandfonline.com/doi/full/10.2217/epi-2016-0069

Acknowledgements

The dataset supporting the conclusions of this article is available in the NCBI Gene Expression Omnibus repository, GSE68456, (www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE68456). The authors thank the BC Children’s & Women’s Hospital staff for their help with subject recruitment; R Jiang, M Ladd, J MacIsaac and M Peñaherrera for their work in sample processing; and L Xu for flow cytometer operation.

Financial & competing interests disclosure

This research was funded by grants from the Canadian Institutes of Health Research (CIHR; MOP-123478 to PM Lavoie and MOP-49520 to WP Robinson). OM de Goede is supported by a CIHR Frederick Banting and Charles Best Graduate Scholarship – Master’s Award. PM Lavoie is supported by a Clinician-Scientist Award from the Child & Family Research Institute and a Career Investigator Award from the Michael Smith Foundation for Health Research. WP Robinson is supported by an investigator award from the Child & Family Research Institute. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

The authors state that they have obtained appropriate institutional review board approval from the University of British Columbia Children’s and Women’s Research Ethics Board (certificate numbers H07-02681 and H04-70488). Written, informed parental consent to participate was obtained. Individual patient data are not reported.

Additional information

Funding

This research was funded by grants from the Canadian Institutes of Health Research (CIHR; MOP-123478 to PM Lavoie and MOP-49520 to WP Robinson). OM de Goede is supported by a CIHR Frederick Banting and Charles Best Graduate Scholarship – Master’s Award. PM Lavoie is supported by a Clinician-Scientist Award from the Child & Family Research Institute and a Career Investigator Award from the Michael Smith Foundation for Health Research. WP Robinson is supported by an investigator award from the Child & Family Research Institute. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.