DNA Methylation Dynamics during In Vivo Differentiation of Blood and Skin Stem Cells

SummaryDNA methylation is a mechanism of epigenetic regulation that is common to all vertebrates. Functional studies underscore its relevance for tissue homeostasis, but the global dynamics of DNA methylation during in vivo differentiation remain underexplored. Here we report high-resolution DNA methylation maps of adult stem cell differentiation in mouse, focusing on 19 purified cell populations of the blood and skin lineages. DNA methylation changes were locus specific and relatively modest in magnitude. They frequently overlapped with lineage-associated transcription factors and their binding sites, suggesting that DNA methylation may protect cells from aberrant transcription factor activation. DNA methylation and gene expression provided complementary information, and combining the two enabled us to infer the cellular differentiation hierarchy of the blood lineage directly from genome-scale data. In summary, these results demonstrate that in vivo differentiation of adult stem cells is associated with small but informative changes in the genomic distribution of DNA methylation.

Graphical AbstractFigure optionsDownload full-size imageDownload high-quality image (113 K)Download as PowerPoint slideHighlights► Genomic DNA methylation maps for 19 purified cell types of blood and skin lineages ► Myeloid transcription factors and binding sites become methylated in lymphoid cells ► Adult stem cells retain low DNA methylation at regulatory regions of other lineages ► Epigenome and transcriptome enable inference of the blood differentiation hierarchy