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Bocker MT, Hellwig M, Breiling A, Eckstein V, Ho AD, Lyko F.. Genome-wide promoter DNA methylation dynamics of human hematopoietic progenitor cells during differentiation and aging. Blood 117: e182-e189

Division of Epigenetics, DKFZ-ZMBH Alliance, German Cancer Research Center, Heidelberg, Germany.
Blood (Impact Factor: 10.45). 03/2011; 117(19):e182-9. DOI: 10.1182/blood-2011-01-331926
Source: PubMed

ABSTRACT

DNA methylation plays an important role in the self-renewal of hematopoietic stem cells and in the commitment to the lymphoid or myeloid lineages. Using purified CD34⁺ hematopoietic progenitor cells and differentiated myeloid cell populations from the same human samples, we obtained detailed methylation profiles at distinct stages of hematopoiesis. We identified a defined set of differentiation-related genes that are methylated in CD34⁺ hematopoietic progenitor cells but show pronounced DNA hypomethylation in monocytes and in granulocytes. In addition, by comparing hematopoietic progenitor cells from umbilical cord blood to hematopoietic progenitor cells from peripheral blood of adult donors we were also able to analyze age-related methylation changes in CD34⁺ cells. Interestingly, the methylation changes observed in older progenitor cells showed a bimodal pattern with hypomethylation of differentiation-associated genes and de novo methylation events resembling epigenetic mutations. Our results thus provide detailed insight into the methylation dynamics during differentiation and suggest that epigenetic changes contribute to hematopoietic progenitor cell aging.

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Available from: Achim Breiling, Jul 22, 2015
    • "Subsequently, de novo DNA methylation of dividing cells establishes the CpG methylation marks that guide restriction of gene expression patterns associated with tissue-specific lineages (Smith et al. 2012). In adult tissues, CpG methylation marks must also be maintained by DNA methyl-transferases during DNA replication to preserve the identity and function of differentiating cell types and for self-renewal of adult stem cell populations (Trowbridge and Orkin 2010;Bocker et al. 2011; Berdasco and Esteller 2010). Taking only into account the information content of alternatively spliced sites (ASSs) with consensus sequences like 5′ splice sites, 3′ splice sites, and branch sites is insufficient for splice site selection (). "
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    • "This indicates that muscle stem cells do not lose their differentiation potency with age, suggesting that the decrease with aging in the differentiation program during muscle regeneration is strongly related to changes in circulating factors. DNA methylation has been shown to be increased in several tissues with aging, and the skeletal muscle is no exception [119] [120]. We have observed a higher level of DNA methylation in satellite cells of aged subjects (unpublished data). "
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    • "Two studies have analyzed DNA methylation during aging in human adult stem cells: Bork et al. (2010) used 27K methylation arrays to analyze the DNA methylation status of mesenchymal stem cells (MSCs) obtained from young (21–50 yr) and old donors (53– 85 yr) and found similar DNA methylation changes over time during prolonged in vitro culture and in vivo aging. Using the same methylation arrays, Bocker et al. (2011) observed a bimodal pattern of methylation changes in older hematopoietic progenitor cells, with hypomethylation of differentiation-associated genes, as well as de novo methylation events resembling epigenetic mutations . Recent studies in mice have revealed a number of genomewide alterations in DNA methylation (Taiwo et al. 2013) that might play an important role in the functional decline of hematopoietic stem cells (HSCs) during aging (Beerman et al. 2013). "

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