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Bocker, M.T.; Hellwig, I.; Breiling, A.; Eckstein, V.; Ho, A.D.; Lyko, F. |
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Title |
Genome-wide promoter DNA methylation dynamics of human hematopoietic progenitor cells during differentiation and aging |
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Journal Article |
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Year |
2011 |
Publication |
Blood |
Abbreviated Journal |
Blood |
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Volume |
117 |
Issue |
19 |
Pages |
e182-189 |
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Keywords |
Adult; Aging/*genetics; Cell Differentiation/*genetics; Cell Separation; DNA Methylation/*genetics; Flow Cytometry; Genome-Wide Association Study; Hematopoiesis/*genetics; Hematopoietic Stem Cells/*cytology; Humans; Oligonucleotide Array Sequence Analysis; Promoter Regions, Genetic/*genetics |
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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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1528-0020 |
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WP5 In vitro |
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PMID: 21427290 |
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UNIBAS @ david.schuermann @ Bocker2011 |
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71 |
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Chen, G.; Upham, B.L.; Sun, W.; Chang, C.C.; Rothwell, E.J.; Chen, K.M.; Yamasaki, H.; Trosko, J.E. |
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Title |
Effect of electromagnetic field exposure on chemically induced differentiation of friend erythroleukemia cells |
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Journal Article |
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Year |
2000 |
Publication |
Environmental health perspectives |
Abbreviated Journal |
Environ Health Perspect |
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108 |
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10 |
Pages |
967-972 |
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Cell Differentiation/*physiology; Cell Division; *Cell Transformation, Neoplastic; Electromagnetic Fields/*adverse effects; *Friend murine leukemia virus; Humans; Leukemia, Erythroblastic, Acute/*pathology; Telomerase/metabolism; Tumor Cells, Cultured |
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Abstract |
Whether exposure of humans to extremely low frequency electromagnetic fields (ELF-EMF) can cause cancer is controversial and therefore needs further research. We used a Friend erythroleukemia cell line that can be chemically induced to differentiate to determine whether ELF-EMF could alter proliferation and differentiation in these cells in a manner similar to that of a chemical tumor promoter. Exposure of this cell line to 60 Hz ELF-EMF resulted in a dose dependent inhibition of differentiation, with maximal inhibition peaking at 40% and 40 mG (4 microT). ELF-EMF at 10 mG (1.0 microT) and 25 mG (2.5 microT) inhibited differentiation at 0 and 20%, respectively. ELF-EMF at 1.0 (100) and 10.0 G (1,000 microT) stimulated cell proliferation 50% above the sham-treated cells. The activity of telomerase, a marker of undifferentiated cells, decreased 100[times] when the cells were induced to differentiate under sham conditions, but when the cells were exposed to 0.5 G (50 microT) there was only a 10[times] decrease. In summary, ELF-EMF can partially block the differentiation of Friend erythroleukemia cells, and this results in a larger population of cells remaining in the undifferentiated, proliferative state, which is similar to the published results of Friend erythroleukemia cells treated with chemical-tumor promoters. |
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0091-6765 |
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WP5 In vitro |
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PMID: 11049817 |
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UNIBAS @ david.schuermann @ Chen2000 |
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72 |
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Czyz, J.; Nikolova, T.; Schuderer, J.; Kuster, N.; Wobus, A.M. |
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Non-thermal effects of power-line magnetic fields (50 Hz) on gene expression levels of pluripotent embryonic stem cells-the role of tumour suppressor p53 |
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Journal Article |
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2004 |
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Mutation research |
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Mutat Res |
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557 |
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1 |
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63-74 |
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Animals; Cells, Cultured; *Electromagnetic Fields; Embryo, Mammalian/*cytology; Gene Expression Regulation/*radiation effects; Genes, Regulator; Mice; Pluripotent Stem Cells/metabolism/*radiation effects; Tumor Suppressor Protein p53/physiology |
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The diffusion of extremely low-frequency (50 Hz) electromagnetic fields (ELF-EMF) in the human environment raises the question of the induction of biological effects of EMF on mammalian cells. We used the model of mouse pluripotent embryonic stem (ES) cells, which have the capacity to develop in vitro into cells of all lineages, to analyse non-thermal effects of ELF-EMF. Wild type (wt) and p53-deficient ES cells were exposed under controlled conditions to ELF-EMF signals simulating power-line (50 Hz) magnetic field (PL-MF) exposure. Different flux densities of 0.1 mT, 1.0 mT or 2.3 mT and intermittency schemes with various ON/OFF cycles were applied for 6 h or 48 h during the first stages of cell differentiation. Transcript levels of regulatory genes, such as egr-1, p21, c-jun, c-myc, hsp70 and bcl-2, were analysed by semi-quantitative RT-PCR immediately after exposure or after a recovery time of 18 h. Intermittent PL-MF exposure to 5 min ON/30 min OFF cycles at a flux density of 2.3 mT for 6 h resulted in a significant up-regulation of c-jun, p21 and egr-1 mRNA levels in p53-deficient, but not in wild-type cells. No significant effects were observed in both cell systems by PL-MF at lower flux densities, longer exposure time or after 18 h recovery time. Our data indicate that 5 min ON/30 min OFF intermittent PL-MF exposure is capable of evoking non-thermal responses in ES cells, dependent on the cellular p53 function. The nature of the biological responses triggered by PL-MF is discussed. |
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0027-5107 |
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PMID: 14706519 |
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UNIBAS @ david.schuermann @ Czyz2004 |
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73 |
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COEBERGH, J.; REEDIJK, A.; DEVRIES, E.; MARTOS, C.; JAKAB, Z.; STELIAROVAFOUCHER, E.; KAMPS, W. |
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Title |
Leukaemia incidence and survival in children and adolescents in Europe during 1978–1997. Report from the Automated Childhood Cancer Information System project |
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Journal Article |
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Year |
2006 |
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European Journal of Cancer |
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European Journal of Cancer |
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42 |
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13 |
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2019-2036 |
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0959-8049 |
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WP9 Epidemiology |
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IARC @ ErdmannF @ |
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85 |
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Author |
Does, M.; Scélo, G.; Metayer, C.; Selvin, S.; Kavet, R.; Buffler, P. |
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Title |
Exposure to Electrical Contact Currents and the Risk of Childhood Leukemia |
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Journal Article |
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Year |
2011 |
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Radiation Research |
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Radiation Research |
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175 |
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3 |
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390-396 |
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0033-7587 |
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IARC @ ErdmannF @ |
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86 |
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