Genome-wide promoter DNA methylation dynamics of human hematopoietic progenitor cells during differentiation and aging.

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.

journal_name

Blood

journal_title

Blood

authors

Bocker MT,Hellwig I,Breiling A,Eckstein V,Ho AD,Lyko F

doi

10.1182/blood-2011-01-331926

subject

Has Abstract

pub_date

2011-05-12 00:00:00

pages

e182-9

issue

19

eissn

0006-4971

issn

1528-0020

pii

blood-2011-01-331926

journal_volume

117

pub_type

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