Methylome Analysis of Human Bone Marrow MSCs Reveals Extensive Age- and Culture-Induced Changes at Distal Regulatory Elements

• DOI: 10.1016/j.stemcr.2017.07.018
• Publication Date: 2017-08-25T01:48:06Z
• Authors: Kalyan K. Pasumarthy; Naresh Doni Jayavelu; Lotta Kilpinen; Colin Andrus; Stephanie L. Battle; Matti Korhonen; Petri Lehenkari; Riikka Lund; Saara Laitinen; R. David Hawkins
• Keywords: CpG site

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 of BM-MSCs induce epigenetic changes that can impact therapeutic outcomes. By applying sequencing-based methods, we reveal the breadth DNA methylation dynamics associated with aging is greater than previously reported. Methylation are enriched at known distal transcription factor binding sites such enhancer elements, instead CpG-rich regions, gene expression. From this, constructed hypo- hypermethylation-specific regulatory networks, including a sub-network BM-MSC master regulators their predicted target genes, identified putatively disrupted signaling pathways. Our genome-wide analyses provide broader overview age- expansion-induced better understanding extent which these alter expression functionality human BM-MSCs.