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Aging and disease    2019, Vol. 10 Issue (1) : 174-189     DOI: 10.14336/AD.2017.1213
Review |
Epigenetic Regulation of Bone Marrow Stem Cell Aging: Revealing Epigenetic Signatures associated with Hematopoietic and Mesenchymal Stem Cell Aging
Dimitrios Cakouros1,2, Stan Gronthos1,2,*
1Mesenchymal Stem Cell Laboratory, Adelaide Medical School, Faculty of Health and Medical Sciences, University of Adelaide, Adelaide, SA, Australia.
2South Australian Health and Medical Research Institute, Adelaide, SA, Australia.
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Abstract  

In this review we explore the importance of epigenetics as a contributing factor for aging adult stem cells. We summarize the latest findings of epigenetic factors deregulated as adult stem cells age and the consequence on stem cell self-renewal and differentiation, with a focus on adult stem cells in the bone marrow. With the latest whole genome bisulphite sequencing and chromatin immunoprecipitations we are able to decipher an emerging pattern common for adult stem cells in the bone marrow niche and how this might correlate to epigenetic enzymes deregulated during aging. We begin by briefly discussing the initial observations in yeast, drosophila and Caenorhabditis elegans (C. elegans) that led to the breakthrough research that identified the role of epigenetic changes associated with lifespan and aging. We then focus on adult stem cells, specifically in the bone marrow, which lends strong support for the deregulation of DNA methyltransferases, histone deacetylases, acetylates, methyltransferases and demethylases in aging stem cells, and how their corresponding epigenetic modifications influence gene expression and the aging phenotype. Given the reversible nature of epigenetic modifications we envisage “epi” targeted therapy as a means to reprogram aged stem cells into their younger counterparts.

Keywords histone      chromatin      HSC      MSC      methylation     
Corresponding Authors: Gronthos Stan   
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These authors contributed equally.

Issue Date: 02 November 2017
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Cakouros Dimitrios,Gronthos Stan. Epigenetic Regulation of Bone Marrow Stem Cell Aging: Revealing Epigenetic Signatures associated with Hematopoietic and Mesenchymal Stem Cell Aging[J]. Aging and disease, 2019, 10(1): 174-189.
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http://www.aginganddisease.org/EN/10.14336/AD.2017.1213     OR     http://www.aginganddisease.org/EN/Y2019/V10/I1/174
Figure 1.  Age Associated Epigenetic Changes in Organisms. Histone and DNA modification marks associated with aging in different species is shown as well as their associated epigenetic enzymes. The effect on aging and lifespan is also shown.
Figure 2.  Age Associated Epigenetic Changes in Aged HSC/MSC. Histone and DNA modification marks in aged HSC and MSC are shown as well as their associated epigenetic enzymes. The effect on HSC/MSC aging is shown.
Figure 3.  Chromatin Structure of Stemness and differentiation genes in Aged HSC/MSC. Histone and DNA modification marks in aged HSC and MSC consist of DNA methylation, H3K9me3 and H3K27me3 being more abundant along lineage/differentiation promoters therefore inhibiting transcription and differentiation. This is more apparent on lymphoid genes in HSC therefore skewing differentiation towards the myeloid lineage. Stemness genes contain an abundance of active marks such as H3K4me1, H3K4me3 and H3K27Ac leading to an open chromatin conformation and keeping the adult stem cells in an immature state.
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