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DNA methylation analysis of murine hematohematopoietic side population cells during aging

Taiwo, O; Wilson, GA; Emmett, W; Morris, T; Bonnet, D; Schuster, E; Adejumo, T; ... Pearce, DJ; + view all (2013) DNA methylation analysis of murine hematohematopoietic side population cells during aging. Epigenetics , 8 (10) pp. 1114-1122. 10.4161/epi.26017. Green open access

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Abstract

Stem cells have been found in most tissues/organs. These somatic stem cells produce replacements for lost and damaged cells, and it is not completely understood how this regenerative capacity becomes diminished during aging. To study the possible involvement of epigenetic changes in somatic stem cell aging, we used murine hematohematopoiesis as a model system. HematoHematopoietic stem cells (HSCs) were enriched for via Hoechst exclusion activity (SP-HSC) from young, medium-aged and old mice and subjected to comprehensive, global methylome (MeDIP-seq) analysis. With age, we observed a global loss of DNA methylation of approximately 5%, but an increase in methylation at some CpG islands. Just over 100 significant (FDR < 0.2) aging-specific differentially methylated regions (aDMRs) were identified, which are surprisingly few considering the profound age-based changes that occur in HSC biology. Interestingly, the polycomb repressive complex -2 (PCRC2) target genes Kiss1r, Nav2 and Hsf4 were hypermethylated with age. The promoter for the Sdpr gene was determined to be progressively hypomethylated with age. This occurred concurrently with an increase in gene expression with age. To explore this relationship further, we cultured isolated SP-HSC in the presence of 5-aza-deoxycytdine and demonstrated a negative correlation between Sdpr promoter methylation and gene expression. We report that DNA methylation patterns are well preserved during hematohematopoietic stem cell aging, confirm that PCRC2 targets are increasingly methylated with age, and suggest that SDPR expression changes with age in HSCs may be regulated via age-based alternations in DNA methylation.

Type: Article
Title: DNA methylation analysis of murine hematohematopoietic side population cells during aging
Open access status: An open access version is available from UCL Discovery
DOI: 10.4161/epi.26017
Publisher version: http://dx.doi.org/10.4161/epi.26017
Language: English
Additional information: © 2013 Landes Bioscience. This is an open-access article licensed under a Creative Commons Attribution 3.0 Unported License. The article may be redistributed, reproduced, and reused, provided the original source is properly cited.
Keywords: DNA methylation, Hsf4, Kiss1r, Nano-MeDIP-seq, Nav2, Sdpr polycomb repressive complex -2 (PCRC2), Aging, Epigenetics, Hematopoietic stem cells, Methylome, Methylomics
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute > Research Department of Cancer Bio
URI: https://discovery.ucl.ac.uk/id/eprint/1406698
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