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DNA methylation profiling reveals differences in the 3 human monocyte subsets and identifies uremia to induce DNA methylation changes during differentiation
- Source :
- Zawada, A M, Schneider, J S, Michel, A I, Rogacev, K S, Hummel, B, Krezdorn, N, Müller, S, Rotter, B, Winter, P, Obeid, R, Geisel, J, Fliser, D & Heine, G H 2016, ' DNA methylation profiling reveals differences in the 3 human monocyte subsets and identifies uremia to induce DNA methylation changes during differentiation ', Epigenetics, vol. 11, no. 4, pp. 259-72 . https://doi.org/10.1080/15592294.2016.1158363
- Publication Year :
- 2016
-
Abstract
- Human monocytes are a heterogeneous cell population consisting of 3 subsets: classical CD14++CD16-, intermediate CD14++CD16+ and nonclassical CD14+CD16++ monocytes. Via poorly characterized mechanisms, intermediate monocyte counts rise in chronic inflammatory diseases, among which chronic kidney disease is of particular epidemiologic importance. DNA methylation is a central epigenetic feature that controls hematopoiesis. By applying next-generation Methyl-Sequencing we now tested how far the 3 monocyte subsets differ in their DNA methylome and whether uremia induces DNA methylation changes in differentiating monocytes. We found that each monocyte subset displays a unique phenotype with regards to DNA methylation. Genes with differentially methylated promoter regions in intermediate monocytes were linked to distinct immunological processes, which is in line with results from recent gene expression analyses. In vitro, uremia induced dysregulation of DNA methylation in differentiating monocytes, which affected several transcription regulators important for monocyte differentiation (e.g., FLT3, HDAC1, MNT) and led to enhanced generation of intermediate monocytes. As potential mediator, the uremic toxin and methylation inhibitor S-adenosylhomocysteine induced shifts in monocyte subsets in vitro, and associated with monocyte subset counts in vivo. Our data support the concept of monocyte trichotomy and the distinct role of intermediate monocytes in human immunity. The shift in monocyte subsets that occurs in chronic kidney disease, a proinflammatory condition of substantial epidemiological impact, may be induced by accumulation of uremic toxins that mediate epigenetic dysregulation.
- Subjects :
- 0301 basic medicine
Cancer Research
CD14
Cellular differentiation
Lipopolysaccharide Receptors
Histone Deacetylase 1
Biology
GPI-Linked Proteins
Monocytes
03 medical and health sciences
medicine
Humans
Epigenetics
Renal Insufficiency, Chronic
Molecular Biology
Uremia
Regulation of gene expression
Basic Helix-Loop-Helix Leucine Zipper Transcription Factors
Monocyte
Receptors, IgG
High-Throughput Nucleotide Sequencing
Cell Differentiation
Methylation
DNA Methylation
S-Adenosylhomocysteine
Healthy Volunteers
Repressor Proteins
030104 developmental biology
medicine.anatomical_structure
Gene Expression Regulation
fms-Like Tyrosine Kinase 3
Monocyte differentiation
DNA methylation
Cancer research
Research Paper
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Journal :
- Zawada, A M, Schneider, J S, Michel, A I, Rogacev, K S, Hummel, B, Krezdorn, N, Müller, S, Rotter, B, Winter, P, Obeid, R, Geisel, J, Fliser, D & Heine, G H 2016, ' DNA methylation profiling reveals differences in the 3 human monocyte subsets and identifies uremia to induce DNA methylation changes during differentiation ', Epigenetics, vol. 11, no. 4, pp. 259-72 . https://doi.org/10.1080/15592294.2016.1158363
- Accession number :
- edsair.doi.dedup.....2d460a2274c270fc6f2f72efc35a12fc