![Sample our Bioscience journals, sign in here to start your access, Latest two full volumes FREE to you for 14 days]({"type":"image" , "src" : "/sda/5925/TOC-Subject-Sample-2021-Bioscience.jpg"})
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 hematopoiesis as a model system. Hematopoietic 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 hematopoietic 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 alterations in DNA methylation.
Disclosure of Potential Conflicts of Interest
No potential conflicts of interest were disclosed.
Acknowledgments
OT was supported by a PhD studentship from the UK Medical Research Council. The experimental part was supported by EU-FP7 project IDEAL-HEALTH-2010–259679. DP was supported by The Royal Society (RG2009/R1), EU-FP7 project IDEAL (259679), and the BBSRC (56102). Research in the Beck laboratory was supported by: Wellcome Trust (084071), Royal Society Wolfson Research Merit Award (WM100023) and EU-FP7 projects IDEAL (259679), EPIGENESYS (257082), and BLUEPRINT (282510). We thank all the staff of UCL Biological Service Unit, UCL Genomics as well as Dr Ayad Eddaoudi of the ICH FACS Laboratory for technical assistance.
Author Contributions
OT, DJP, and SB conceived the study. OT performed the experiments. GAW and WE did the bioinformatics and statistical analysis. OT, GAW, WE, and, TM analyzed data. DB, DJP, and SB contributed materials. OT, TA, and DJP performed FACS analysis. OT, SB, and DJP wrote the paper with contributions from all co-authors.
Supplemental Materials
Supplemental materials may be found here: www.landesbioscience.com/journals/epigenetics/article/26017