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Michelle Rönnerblad, Robin Andersson, Tor Olofsson, Iyadh Douagi, Mohsen Karimi, Söen Lehmann, Ilka Hoof, Michiel de Hoon, Masayoshi Itoh, Sayaka Nagao-Sato, Hideya Kawaji, Timo Lassmann, Piero Carninci, Yoshihide Hayashizaki, Alistair R. R. Forrest, Albin Sandelin, Karl Ekwall, Erik Arner, and Andreas Lennartsson |
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Title |
Analysis of the DNA methylome and transcriptome in granulopoiesis reveals timed changes and dynamic enhancer methylation |
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Journal Article |
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2014 |
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Blood |
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123 |
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17 |
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79-89 |
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In development, epigenetic mechanisms such as DNA methylation have been suggested to provide a cellularmemoryto maintain multipotency but also stabilize cell fate decisions and direct lineage restriction. In this study, we set out to characterize changes in DNA methylation and gene expression during granulopoiesis using 4 distinct cell populations ranging from the oligopotent common myeloid progenitor stage to terminally differentiated neutrophils. We observed that differentially methylated sites (DMSs) generally show decreased methylation during granulopoiesis. Methylation appears to change at specific differentiation stages and overlap with changes in transcription and activity of key hematopoietic transcription factors. DMSs were preferentially located in areas distal to CpG islands and shores. Also, DMSs were overrepresented in enhancer elements and enriched in enhancers that become active during differentiation.Overall, this studydepicts in detail the epigenetic and transcriptional changes that occur during granulopoiesis and supports the role of DNA methylation as a regulatory mechanism in blood cell differentiation. |
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UNIBAS @ melissa.manser @ |
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573 |
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Yan, J.; Dong, L.; Zhang, B.; Qi, N. |
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Title |
Effects of extremely low-frequency magnetic field on growth and differentiation of human mesenchymal stem cells |
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Journal Article |
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Year |
2010 |
Publication |
Electromagnetic biology and medicine |
Abbreviated Journal |
Electromagn Biol Med |
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29 |
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4 |
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165-176 |
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Cell Differentiation/*radiation effects; Cell Proliferation/radiation effects; Cell Survival/radiation effects; Electromagnetic Fields/*adverse effects; Humans; Magnetics; Mesenchymal Stem Cells/*cytology/metabolism/*radiation effects; Osmolar Concentration; Osteogenesis/radiation effects; Potassium/metabolism; Sodium/metabolism |
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Human Mesenchymal Stem Cells (hMSCs) were exposed to a developed extremely low-frequency (ELF) magnetic fields (50 Hz ,20 mT ELF) system to evaluate whether exposure to (ELF) magnetic fields affects growth, metabolism, and differentiation of hMSCs. MTT method was used to determine the growth and metabolism of hMSCs following exposure to ELF magnetic fields. Na(+)/K(+) concentration and osmolality of extracellular were measured after exposured culture. Alkaline phosphatase (ALP) assay and Calcium assay, ALP staining, and Alizarin red staining were performed to evaluate the osteogenic differentiation of hMSCs under the ELF magnetic field exposure. In these experiments, the cells were exposed to ELF for up to 23 days. The results showed that exposure to ELF magnetic field could inhibit the growth and metabolism of hMSC, but have no significant effect on differentiation of hMSCs. These results suggested that ELF magnetic field may influence the early development of hMSCs related adult cells. |
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1536-8386 |
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PMID: 20923323 |
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UNIBAS @ david.schuermann @ Yan2010 |
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82 |
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Sarimov, R.; Alipov, E.D.; Belyaev, I.Y. |
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Fifty hertz magnetic fields individually affect chromatin conformation in human lymphocytes: dependence on amplitude, temperature, and initial chromatin state |
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Journal Article |
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2011 |
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Bioelectromagnetics |
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Bioelectromagnetics |
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32 |
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7 |
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570-579 |
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Effects of magnetic field (MF) at 50 Hz on chromatin conformation were studied by the method of anomalous viscosity time dependence (AVTD) in human lymphocytes from two healthy donors. MF within the peak amplitude range of 5-20 microT affected chromatin conformation. These MF effects differed significantly between studied donors, and depended on magnetic flux density and initial condensation of chromatin. While the initial state of chromatin was rather stable in one donor during one calendar year of measurements, the initial condensation varied significantly in cells from another donor. Both this variation and the MF effect depended on temperature during exposure. Despite these variations, the general rule was that MF condensed the relaxed chromatin and relaxed the condensed chromatin. Thus, in this study we show that individual effects of 50 Hz MF exposure at peak amplitudes within the range of 5-20 microT may be observed in human lymphocytes in dependence on the initial state of chromatin and temperature. |
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1521-186X |
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PMID: 21500233 |
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UNIBAS @ david.schuermann @ Sarimov2011 |
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81 |
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Ramirez, J.; Lukin, K.; Hagman, J. |
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Title |
From hematopoietic progenitors to B cells: mechanisms of lineage restriction and commitment |
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Journal Article |
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2010 |
Publication |
Current opinion in immunology |
Abbreviated Journal |
Curr Opin Immunol |
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22 |
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2 |
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177-184 |
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Animals; Antigens, Differentiation/genetics/immunology; B-Lymphocytes/*immunology; *Cell Lineage; Epigenesis, Genetic/immunology; Gene Expression Regulation, Developmental; Hematopoietic Stem Cells/*immunology; Humans; *Lymphopoiesis; Transcription Factors/*immunology |
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The generation of B lymphocytes from hematopoietic progenitors requires lineage-specific transcription factors that progressively direct cell fate choices. Differentiation of hematopoietic stem cells to lymphoid progenitors requires Ikaros-dependent lineage priming and graded levels of PU.1, which are controlled by Ikaros and Gfi1. E2A drives expression of EBF1, which initiates B lineage specification. EBF1, in addition to Pax5, is necessary for commitment to the B cell lineage. As a model of gene activation in early B lymphopoiesis, mb-1 genes are activated sequentially by factors (e.g. EBF1) that initiate chromatin modifications before transcription. This review highlights the requisite interplay between transcription factors and epigenetic mechanisms in the context of B cell development. |
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1879-0372 |
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PMID: 20207529 |
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UNIBAS @ david.schuermann @ Ramirez2010 |
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80 |
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Nikolova, T.; Czyz, J.; Rolletschek, A.; Blyszczuk, P.; Fuchs, J.; Jovtchev, G.; Schuderer, J.; Kuster, N.; Wobus, A.M. |
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Electromagnetic fields affect transcript levels of apoptosis-related genes in embryonic stem cell-derived neural progenitor cells |
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Journal Article |
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2005 |
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The FASEB journal : official publication of the Federation of American Societies for Experimental Biology |
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Faseb J |
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19 |
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12 |
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1686-1688 |
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*Apoptosis; Cell Proliferation; Comet Assay; DNA/chemistry; DNA Damage; Down-Regulation; *Electromagnetic Fields; Embryo, Mammalian/*cytology; *Embryo, Nonmammalian; Intracellular Signaling Peptides and Proteins/metabolism; Models, Biological; Neurons/metabolism/*radiation effects; Protein Biosynthesis; Protein Processing, Post-Translational; Proto-Oncogene Proteins c-bcl-2/metabolism; RNA, Messenger/metabolism; Reverse Transcriptase Polymerase Chain Reaction; Stem Cells/*cytology/*radiation effects; Time Factors; Transcription, Genetic/*radiation effects; Up-Regulation; bcl-2-Associated X Protein/metabolism |
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Mouse embryonic stem (ES) cells were used as an experimental model to study the effects of electromagnetic fields (EMF). ES-derived nestin-positive neural progenitor cells were exposed to extremely low frequency EMF simulating power line magnetic fields at 50 Hz (ELF-EMF) and to radiofrequency EMF simulating the Global System for Mobile Communication (GSM) signals at 1.71 GHz (RF-EMF). Following EMF exposure, cells were analyzed for transcript levels of cell cycle regulatory, apoptosis-related, and neural-specific genes and proteins; changes in proliferation; apoptosis; and cytogenetic effects. Quantitative RT-PCR analysis revealed that ELF-EMF exposure to ES-derived neural cells significantly affected transcript levels of the apoptosis-related bcl-2, bax, and cell cycle regulatory “growth arrest DNA damage inducible” GADD45 genes, whereas mRNA levels of neural-specific genes were not affected. RF-EMF exposure of neural progenitor cells resulted in down-regulation of neural-specific Nurr1 and in up-regulation of bax and GADD45 mRNA levels. Short-term RF-EMF exposure for 6 h, but not for 48 h, resulted in a low and transient increase of DNA double-strand breaks. No effects of ELF- and RF-EMF on mitochondrial function, nuclear apoptosis, cell proliferation, and chromosomal alterations were observed. We may conclude that EMF exposure of ES-derived neural progenitor cells transiently affects the transcript level of genes related to apoptosis and cell cycle control. However, these responses are not associated with detectable changes of cell physiology, suggesting compensatory mechanisms at the translational and posttranslational level. |
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1530-6860 |
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PMID: 16116041 |
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UNIBAS @ david.schuermann @ Nikolova2005 |
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79 |
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