GSE114254
The adult haematopoietic stem cell CpG island methylome is almost entirely recapitulated in progeny cells: Implications for disease
Background Differences in immune response between individuals is driven in part by epigenetic factors. To understand the contribution of DNA methylation to these differences, we have investigated the role of haematopoietic stem cell methylation in driving variation in daughter cell differentiation and state. Methods Haematopoietic cells (namely CD34+, CD14+ and CD56+) were isolated from peripheral blood of 11 healthy individuals and subject to modified reduced representation bisulfite sequencing. DNA methylation was profiled and compared at CpG islands. Results DNA methylation state is almost entirely recapitulated between progenitor and progeny haematopoietic cells. Fewer differences in DNA methylation were detected between haematopoietic cells than between haematopoietic cells and buccal mucosa. Cell subset differences in methylation were over-represented near genes important in cell lineage specific maturation and function. Methylation differences between individuals at specific CpG islands were generally small. The CpG islands that varied most between individuals consistently across subsets, were associated with several genes, but were not enriched with regard to specific biological processes. Conclusions Overall, this study suggests that the predominant DNA methylation setting in haematopoietic stem cells is transmitted to progeny cells, with differences between cell subsets and between individuals that are likely to be important in immune cell development and variation in response to pathogens and disease. Our findings provide a plausible mechanism by which genetic and environmental factors may contribute to the development of disease via unfavourable DNA methylation settings. Overall design: 33 samples (11 individuals, each with 3 cell subsets) were analysed