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.
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 |
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
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.