AI Article Synopsis
- DNA methylation is crucial for the self-renewal and lineage commitment of hematopoietic stem cells, influencing their development into lymphoid or myeloid cells.
- Detailed methylation profiles of purified CD34⁺ progenitor cells and differentiated myeloid cells reveal that specific genes are methylated in progenitor cells but become hypomethylated as they differentiate into monocytes and granulocytes.
- Comparing umbilical cord blood and adult peripheral blood progenitor cells highlights age-related DNA methylation changes, showing a bimodal pattern of hypomethylation and new methylation events that indicate potential epigenetic mutations linked to aging in these cells.
Article 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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| http://dx.doi.org/10.1182/blood-2011-01-331926 | DOI Listing |
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