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1000 Titel
  • PRDM8 reveals aberrant DNA methylation in aging syndromes and is relevant for hematopoietic and neuronal differentiation
1000 Autor/in
  1. Cypris, Olivia |
  2. Eipel, Monika |
  3. Franzen, Julia |
  4. Rösseler, Corinna |
  5. Tharmapalan, Vithurithra |
  6. Kuo, Chao-Chung |
  7. Vieri, Margherita |
  8. Nikolić, Miloš |
  9. Kirschner, Martin |
  10. Brümmendorf, Tim H. |
  11. Zenke, Martin |
  12. Lampert, Angelika |
  13. Beier, Fabian |
  14. Wagner, Wolfgang |
1000 Erscheinungsjahr 2020
1000 Publikationstyp
  1. Artikel |
1000 Online veröffentlicht
  • 2020-08-20
1000 Erschienen in
1000 Quellenangabe
  • 12(1):125
1000 Copyrightjahr
  • 2020
1000 Lizenz
1000 Verlagsversion
  • https://doi.org/10.1186/s13148-020-00914-5 |
  • https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7439574/ |
1000 Publikationsstatus
1000 Sprache der Publikation
1000 Abstract/Summary
  • Background!#!Dyskeratosis congenita (DKC) and idiopathic aplastic anemia (AA) are bone marrow failure syndromes that share characteristics of premature aging with severe telomere attrition. Aging is also reflected by DNA methylation changes, which can be utilized to predict donor age. There is evidence that such epigenetic age predictions are accelerated in premature aging syndromes, but it is yet unclear how this is related to telomere length. DNA methylation analysis may support diagnosis of DKC and AA, which still remains a challenge for these rare diseases.!##!Results!#!In this study, we analyzed blood samples of 70 AA and 18 DKC patients to demonstrate that their epigenetic age predictions are overall increased, albeit not directly correlated with telomere length. Aberrant DNA methylation was observed in the gene PRDM8 in DKC and AA as well as in other diseases with premature aging phenotype, such as Down syndrome and Hutchinson-Gilford-Progeria syndrome. Aberrant DNA methylation patterns were particularly found within subsets of cell populations in DKC and AA samples as measured with barcoded bisulfite amplicon sequencing (BBA-seq). To gain insight into the functional relevance of PRDM8, we used CRISPR/Cas9 technology to generate induced pluripotent stem cells (iPSCs) with heterozygous and homozygous knockout. Loss of PRDM8 impaired hematopoietic and neuronal differentiation of iPSCs, even in the heterozygous knockout clone, but it did not impact on epigenetic age.!##!Conclusion!#!Taken together, our results demonstrate that epigenetic aging is accelerated in DKC and AA, independent from telomere attrition. Furthermore, aberrant DNA methylation in PRDM8 provides another biomarker for bone marrow failure syndromes and modulation of this gene in cellular subsets may be related to the hematopoietic and neuronal phenotypes observed in premature aging syndromes.
1000 Sacherschließung
lokal DNA Methylation/genetics [MeSH]
lokal Hematopoietic Stem Cells/metabolism [MeSH]
lokal Dyskeratosis Congenita/genetics [MeSH]
lokal Anemia, Aplastic/blood [MeSH]
lokal Anemia, Aplastic/genetics [MeSH]
lokal Aging and Development Epigenetics
lokal PRDM8
lokal Telomere/metabolism [MeSH]
lokal DNA-Binding Proteins/blood [MeSH]
lokal Hematopoietic differentiation
lokal DNA-Binding Proteins/genetics [MeSH]
lokal Aging
lokal Telomere
lokal Male [MeSH]
lokal Histone Methyltransferases/genetics [MeSH]
lokal DNA methylation
lokal Phenotype [MeSH]
lokal Neuronal differentiation
lokal Epigenetic clock
lokal Female [MeSH]
lokal Humans [MeSH]
lokal Neurons/metabolism [MeSH]
lokal Dyskeratosis congenita
lokal iPSC
lokal Aplastic anemia
lokal Research
lokal Histone Methyltransferases/blood [MeSH]
lokal Dyskeratosis Congenita/blood [MeSH]
1000 Liste der Beteiligten
  1. https://frl.publisso.de/adhoc/uri/Q3lwcmlzLCBPbGl2aWE=|https://frl.publisso.de/adhoc/uri/RWlwZWwsIE1vbmlrYQ==|https://frl.publisso.de/adhoc/uri/RnJhbnplbiwgSnVsaWE=|https://frl.publisso.de/adhoc/uri/UsO2c3NlbGVyLCBDb3Jpbm5h|https://frl.publisso.de/adhoc/uri/VGhhcm1hcGFsYW4sIFZpdGh1cml0aHJh|https://frl.publisso.de/adhoc/uri/S3VvLCBDaGFvLUNodW5n|https://frl.publisso.de/adhoc/uri/VmllcmksIE1hcmdoZXJpdGE=|https://frl.publisso.de/adhoc/uri/Tmlrb2xpxIcsIE1pbG-FoQ==|https://frl.publisso.de/adhoc/uri/S2lyc2NobmVyLCBNYXJ0aW4=|https://frl.publisso.de/adhoc/uri/QnLDvG1tZW5kb3JmLCBUaW0gSC4=|https://frl.publisso.de/adhoc/uri/WmVua2UsIE1hcnRpbg==|https://frl.publisso.de/adhoc/uri/TGFtcGVydCwgQW5nZWxpa2E=|https://frl.publisso.de/adhoc/uri/QmVpZXIsIEZhYmlhbg==|https://orcid.org/0000-0002-1971-3217
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1000 Erstellt am 2023-05-12T15:18:22.042+0200
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1000 Zuletzt bearbeitet Tue Oct 24 08:08:22 CEST 2023
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