Abstract
Mesenchymal stem cells (MSCs), which can differentiate into tri-lineage (osteoblast, adipocyte, and chondrocyte) and suppress inflammation, are promising tools for regenerative medicine. MSCs are phenotypically diverse based on their tissue origins. However, the mechanisms underlying cell-type-specific gene expression patterns are not fully understood due to the lack of suitable strategy to identify the diversity. In this study, we investigated gene expression programs and chromatin accessibilities of MSCs by whole-transcriptome RNA-seq analysis and an assay for transposase-accessible chromatin using sequencing (ATAC-seq). We isolated MSCs from four tissues (femoral and vertebral bone marrow, adipose tissue, and lung) and analysed their molecular signatures. RNA-seq identified the expression of MSC markers and both RNA-seq and ATAC-seq successfully clustered the MSCs based on their tissue origins. Interestingly, clustering based on tissue origin was more accurate with chromatin accessibility signatures than with transcriptome profiles. Furthermore, we identified transcription factors potentially involved in establishing cell-type specific chromatin structures. Thus, epigenome analysis is useful to analyse MSC identity and can be utilized to characterize these cells for clinical use.
Highlights
Mesenchymal stem cells (MSCs) have unique differentiation potential toward three mesenchymal lineages including osteoblast, adipocyte, and chondrocyte[1,2]
We demonstrated a strategy to profile the molecular signatures associated with the establishment of the diversity of MSCs
Our study directly addressed the fundamental question of how each MSC acquires unique features
Summary
Mesenchymal stem cells (MSCs) have unique differentiation potential toward three mesenchymal lineages including osteoblast, adipocyte, and chondrocyte[1,2]. MSCs were originally isolated from the bone marrow, but recently it was shown that they can be isolated from multiple tissues such as adipose, lung, umbilical cord, or dental pulp[12,13,14] These MSCs with different tissue origins are unique in terms of growth rate, differentiation potential, or cell morphology[15,16]. These cell-type specific gene expression programs are dependent on the well-organized deposition of regulatory proteins www.nature.com/scientificreports/ Such as transcription factors, RNA polymerase, or chromatin remodellers[18,19]. Using cells isolated from different tissues as a model to analyse MSC diversity, we simultaneously assessed chromatin accessibility and the transcriptome of MSCs and showed that compared to transcriptome analysis, chromatin accessibility is a superior indicator for cell type identification. We mapped the regulatory landscape of transcription factors in MSCs to establish cell-type specific gene expression programs
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