Abstract

To provide insight into fetal nucleated red blood cell (nRBC) development using genome-wide DNA methylation (DNAm) profiling. 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). 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. 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.

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