Abstract
Human mesenchymal stem cells (MSCs) are adult multipotent cells that have plasticity and inhabit the stroma of diverse tissues. The potential utility of MSCs has been heavily investigated in the fields of regenerative medicine and cell therapy. However, MSCs represent diverse populations that may depend on the tissue of origin. Thus, the ability to identify specific MSC populations has remained difficult. Using RNA sequencing, we analyzed the whole transcriptomes of bone marrow-derived MSCs (BMs), adipose tissue-derived MSCs (AMs), and tonsil-derived MSCs (TMs). We categorized highly regulated genes from these MSC groups according to functional gene ontology (GO) classification. AMs and TMs showed higher expression of genes encoding proteins that function in protein binding, growth factor, or cytokine activity in extracellular compartments than BMs. Interestingly, TM were highly enriched for genes coding extracellular, protein-binding proteins compared with AMs. Functional Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis also showed differentially enriched signaling pathways between the three MSC groups. Further, we confirmed surface antigens expressed in common and in a tissue-specific manner on BMs, AMs, and TMs by flow cytometry analysis. This study provides comprehensive characteristics of MSCs derived from different tissues to better understand their cellular and molecular biology.
Highlights
Mesenchymal stem cells (MSCs) reside in the stroma of tissues such as bone marrow, fat, dermis, and umbilical cord
By RNA sequencing, an average of 78 million 100-base long reads from mesenchymal stem cells (MSCs) from each tissue type were mapped to the human reference genome, assembled per gene, and condensed into FPKM expression values, which provided a measure of expression levels for each gene mapped against the human MSC transcriptome
We used RNA sequencing (RNA-seq) to characterize the genome-wide expression portrait of human MSCs derived from bone marrow (BMs), adipose tissue (AMs), and palatine tonsil (TMs)
Summary
Mesenchymal stem cells (MSCs) reside in the stroma of tissues such as bone marrow, fat, dermis, and umbilical cord. According to the convention of the International Society for Cellular Therapy (ISCT), MSCs from various sources are defined as being (1) plastic-adherent under standard cell culture conditions; (2) multipotent, i.e., able to differentiate into osteoblasts, adipocytes, and chondrocytes in vitro; and (3) positive for CD73, CD90, and CD105, and negative for CD11b or CD14, CD19 or CD79α, CD34, CD45, and HLA-DR on the cell surface[8] These combinations of positive and negative CDs have been widely accepted as a method for identifying human MSCs. the characterization of MSC based on cell surface marker phenotype is problematic because of variation in the expression of different CD markers displayed by MSCs derived from different tissues[9,10]. Our study provides comparative and comprehensive characterization of MSCs from different tissues of origin
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