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de novo DNA Methylation Balances Hematopoietic Stem Cell Self-Renewal and Differentiation

GSE27322 Mus musculus Methylation profiling by high throughput sequencing; Expression profiling by array 10 samples Submitted 2011/09/30 Platform GPL9250Platform GPL1261
Summary
Cytosine methylation is an epigenetic mark usually associated with gene repression. Despite a requirement for de novo DNA methylation for differentiation of embryonic stem cells, its role in somatic stem cells is unknown. Using conditional ablation, we show that loss of either, or both, Dnmt3a or Dnmt3b, progressively impedes hematopoietic stem cell (HSC) differentiation during serial in vivo passage. Concomitantly, HSC self-renewal is immensely augmented in absence of either Dnmt3, particularly Dnmt3a. Dnmt3-KO HSCs show upregulation of HSC multipotency genes and downregulation of early differentiation factors, and the differentiated progeny of Dnmt3-KO HSCs exhibit hypomethylation and incomplete repression of HSC-specific genes. HSCs lacking Dnmt3a manifest hyper-methylation of CpG islands and hypo-methylation of genes which are highly correlated with human hematologic malignancies. These data establish that aberrant DNA methylation has direct pathologic consequences for somatic stem cell development, leading to inefficient differentiation and maintenance of a self-renewal program.
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Direct links to NCBI, no account and no request form: the whole study as GSE27322_RAW.tar, processed values as the series matrix, the supplementary file directory, and per-sample supplementary files for any of the 10 samples. Raw sequencing reads are also available from ENA.

Also filed as BioProject PRJNA137177 and SRA study SRP005845. Searching any of these in the dataset finder brings you back here.

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