University of Oulu

Pasumarthy, K., Doni Jayavelu, N., Kilpinen, L., Andrus, C., Battle, S., Korhonen, M., Lehenkari, P., Lund, R., Laitinen, S., Hawkins, R. (2017) Methylome Analysis of Human Bone Marrow MSCs Reveals Extensive Age- and Culture-Induced Changes at Distal Regulatory Elements. Stem Cell Reports, 9 (3), 999-1015. doi:10.1016/j.stemcr.2017.07.018

Methylome analysis of human bone marrow MSCs reveals extensive age- and culture-induced changes at distal regulatory elements

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Author: Pasumarthy, Kalyan K.1; Jayavelu, Naresh Doni1,2; Kilpinen, Lotta3;
Organizations: 1Turku Centre for Biotechnology, University of Turku
2Division of Medical Genetics, Department of Medicine, Department of Genome Sciences, Institute for Stem Cell and Regenerative Medicine, University of Washington School of Medicine
3Research and Development, Medical Services, Finnish Red Cross Blood Service
4Cell Therapy Services, Medical Services, Finnish Red Cross Blood Service
5Institute of Clinical Medicine, Division of Surgery and Institute of Biomedicine, Department of Anatomy and Cell Biology, University of Oulu
6Clinical Research Center, Department of Surgery and Intensive Care, Oulu University Hospital
7Åbo Akademi University
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 4.4 MB)
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Language: English
Published: Elsevier, 2017
Publish Date: 2017-11-09


Human bone marrow stromal cells, or mesenchymal stem cells (BM-MSCs), need expansion prior to use as cell-based therapies in immunological and tissue repair applications. Aging and expansion of BM-MSCs induce epigenetic changes that can impact therapeutic outcomes. By applying sequencing-based methods, we reveal that the breadth of DNA methylation dynamics associated with aging and expansion is greater than previously reported. Methylation changes are enriched at known distal transcription factor binding sites such as enhancer elements, instead of CpG-rich regions, and are associated with changes in gene expression. From this, we constructed hypo- and hypermethylation-specific regulatory networks, including a sub-network of BM-MSC master regulators and their predicted target genes, and identified putatively disrupted signaling pathways. Our genome-wide analyses provide a broader overview of age- and expansion-induced DNA methylation changes and a better understanding of the extent to which these changes alter gene expression and functionality of human BM-MSCs.

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Series: Stem cell reports
ISSN: 2213-6711
ISSN-E: 2213-6711
ISSN-L: 2213-6711
Volume: 9
Issue: 3
Pages: 999 - 1015
DOI: 10.1016/j.stemcr.2017.07.018
Type of Publication: A1 Journal article – refereed
Field of Science: 3111 Biomedicine
Funding: This project was supported in part by funding from the Academy of Finland (259913), Biocenter Finland, the NIH, the Washington Life Sciences Discovery Fund (265508), and the SalWe Research Program for IMO (Tekes - the Finnish Funding Agency for Technology and Innovation grant 648/10).
Academy of Finland Grant Number: 259913
Detailed Information: 259913 (Academy of Finland Funding decision)
Dataset Reference: Supplemental Information includes Supplemental Experimental Procedures, six figures, and seven tables and can be found with this article online at: 018
Copyright information: © 2017 The authors. This is an open access article under the CC BY-NC-ND license (