DNA methylation dynamics during in vivo differentiation of blood and skin stem cells

Abstract

DNA 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 genomic 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.


Data and Analysis

Link Description
Cell types and experiments Excel file containing a list of cell types and a summary of DNA methylation mapping experiments
Normalized DNA methylation data Excel file containing DNA methylation levels for 19 cell types and 95,086 genomic regions with sufficient RRBS coverage
Normalized gene expression data Excel file containing gene expression levels for 19 cell types and 20,666 genes based on transcriptome microarrays
Cell-type specific differences Excel file containing significant DNA methylation and gene expression differences between cell types
Blood and skin specific enrichment Excel file detailing the enrichment of genomic properties for blood and skin specific DNA methylation and gene expression
Lymphoid vs. myeloid specific enrichment Excel file detailing the enrichment of genomic properties for lymphoid vs. myeloid specific DNA methylation or gene expression
Blood stem cell specific enrichment Excel file detailing the enrichment of genomic properties for blood stem cell vs. progenitor DNA methylation or gene expression
Skin stem cell specific enrichment Excel file detailing the enrichment of genomic properties for skin stem cells vs. progenitor DNA methylation or gene expression


DNA Methylation Data Visualization and Download

Sample identifier Sample description Raw data: reads and alignments (*) Processed data: single-CpG methylation (**) Visualize in Genome Browser
HSC_1 Hematopoietic stem cell download 1st BAM file, 2nd BAM file download BED file view browser track
HSC_2 Hematopoietic stem cell download 1st BAM file, 2nd BAM file download BED file view browser track
MPP1_1 Multipotent progenitor 1 (Flk2-) download 1st BAM file, 2nd BAM file download BED file view browser track
MPP1_2 Multipotent progenitor 1 (Flk2-) download 1st BAM file, 2nd BAM file download BED file view browser track
MPP2_1 Multipotent progenitor 2 (Flk2+) download 1st BAM file, 2nd BAM file download BED file view browser track
MPP2_2 Multipotent progenitor 2 (Flk2+) download 1st BAM file, 2nd BAM file download BED file view browser track
CLP_1 Common lymphoid progenitor download BAM file download BED file view browser track
CLP_2 Common lymphoid progenitor download BAM file download BED file view browser track
CMP_1 Common myeloid progenitor download BAM file download BED file view browser track
CMP_2 Common myeloid progenitor download BAM file download BED file view browser track
GMP_1 Granulocyte-monocyte progenitor download BAM file download BED file view browser track
GMP_2 Granulocyte-monocyte progenitor download BAM file download BED file view browser track
MEP_1 Megakaryocyte-erythroid progenitor download BAM file download BED file view browser track
MEP_2 Megakaryocyte-erythroid progenitor download BAM file download BED file view browser track
CD4_1 T helper cell (CD4+) download BAM file download BED file view browser track
CD4_2 T helper cell (CD4+) download BAM file download BED file view browser track
CD8_1 Cytotoxic T cell (CD8+) download BAM file download BED file view browser track
CD8_2 Cytotoxic T cell (CD8+) download BAM file download BED file view browser track
B_cell_1 B-cell download BAM file download BED file view browser track
B_cell_2 B-cell download BAM file download BED file view browser track
Eryth_1 Erythrocyte download 1st BAM file, 2nd BAM file download BED file view browser track
Eryth_2 Erythrocyte download 1st BAM file, 2nd BAM file download BED file view browser track
Gran_1 Granulocyte download BAM file download BED file view browser track
Gran_2 Granulocyte download BAM file download BED file view browser track
Mono_1 Monocyte download 1st BAM file, 2nd BAM file download BED file view browser track
Mono_2 Monocyte download 1st BAM file, 2nd BAM file download BED file view browser track
TBSC_1 Telogen (quiescent) bulge stem cell download BAM file download BED file view browser track
TBSC_2 Telogen (quiescent) bulge stem cell download BAM file download BED file view browser track
ABSC_1 Anagen (active) bulge stem cell download BAM file download BED file view browser track
ABSC_2 Anagen (active) bulge stem cell download BAM file download BED file view browser track
MTAC_1 Matrix transient amplifying cell download BAM file download BED file view browser track
MTAC_2 Matrix transient amplifying cell download BAM file download BED file view browser track
CLDC_1 Companion layer differentiated cell download 1st BAM file, 2nd BAM file download BED file view browser track
CLDC_2 Companion layer differentiated cell download 1st BAM file, 2nd BAM file download BED file view browser track
EPro_1 Epidermis progenitor cell download 1st BAM file, 2nd BAM file download BED file view browser track
EPro_2 Epidermis progenitor cell download 1st BAM file, 2nd BAM file download BED file view browser track
EDif_1 Epidermis differentiated cell download 1st BAM file, 2nd BAM file download BED file view browser track
EDif_2 Epidermis differentiated cell download 1st BAM file, 2nd BAM file download BED file view browser track

(*) The unaligned read file can be restored from the BAM files using RevertSam.jar from the Picard software package

(**) All genomic coordinates are relative to the NCBI37/mm9 assembly of the mouse genome


Citation

Bock C, Beerman I, Lien WH, Smith ZD, Gu H, Boyle P, Gnirke A, Fuchs E, Rossi DJ, Meissner A (2012). DNA methylation dynamics during in vivo differentiation of blood and skin stem cells. Mol Cell 47, 633-647.