@article{3087762,
    title = "Sox2 suppression by miR-21 governs human mesenchymal stem cell properties",
    author = "Trohatou, O. and Zagoura, D. and Bitsika, V. and Pappa, K.I. and Antsaklis, A. and Anagnou, N.P. and Roubelakis, M.G.",
    journal = "Stem Cells Translational Medicine",
    year = "2014",
    volume = "3",
    number = "1",
    pages = "54-68",
    publisher = "John Wiley and Sons Ltd",
    issn = "2157-6564, 2157-6580",
    doi = "10.5966/sctm.2013-0081",
    keywords = "green fluorescent protein;  microRNA 21;  octamer transcription factor 4;  peroxisome proliferator activated receptor gamma;  transcription factor NANOG;  transcription factor Sox2, adipogenesis;  amnion fluid;  apoptosis;  article;  bone development;  cell cycle arrest;  cell differentiation;  cell proliferation;  chondrogenesis;  comparative molecular field analysis;  controlled study;  enzyme linked immunosorbent assay;  fibroblast colony forming unit assay;  fluorescence activated cell sorting;  human;  human cell;  immunofluorescence microscopy;  mesenchymal stem cell;  microarray analysis;  MTS proliferation assay;  phenotype;  protein expression;  real time polymerase chain reaction;  upregulation;  Western blotting, Amniotic fluid mesenchymal stem cells;  Bone marrow mesenchymal stem cells;  Cell cycle;  miR-21;  Sox2;  Umbilical cord blood mesenchymal stem cells, 3' Untranslated Regions;  Bone Marrow Cells;  Cell Differentiation;  Cell Proliferation;  Cells, Cultured;  Homeodomain Proteins;  Humans;  Mesenchymal Stromal Cells;  MicroRNAs;  Multipotent Stem Cells;  Octamer Transcription Factor-3;  SOXB1 Transcription Factors;  Transcriptome",
    abstract = "MicroRNAs (miRNAs) have recently been shown to act as regulatory signals for maintaining stemness and for determining the fate of adult and fetal stem cells, such as human mesenchymal stem cells (hMSCs). hMSCs constitute a population of multipotent stem cells that can be expanded easily in culture and are able to differentiate into many lineages. We have isolated two subpopulations of fetal mesenchymal stem cells (MSCs) from amniotic fluid (AF) known as spindle-shaped (SS) and roundshaped (RS) cells and characterized them on the basis of their phenotypes, pluripotency, proliferation rates, and differentiation potentials. In this study, we analyzed the miRNA profile of MSCs derived from AF, bone marrow (BM), and umbilical cord blood (UCB). We initially identified 67 different miRNAs that were expressed in all three types ofMSCs but at different levels, depending on the source. A more detailed analysis revealed that miR-21 was expressed at higher levels in RS-AF-MSCs and BMMSCs compared with SS-AF-MSCs. We further demonstrated for the first time a direct interaction betweenmiR-21 and the pluripotencymarker Sox2. The induction of miR-21 strongly inhibited Sox2 expression in SS-AF-MSCs, resulting in reduced clonogenic and proliferative potential and cell cycle arrest. Strikingly, the opposite effect was observed upon miR-21 inhibition in RS-AF-MSCs and BMMSCs, which led to an enhanced proliferation rate. Finally, miR-21 induction accelerated osteogenesis and impaired adipogenesis and chondrogenesis in SS-AF-MSCs. Therefore, these findings suggest that miR-21 might specifically function by regulating Sox2 expression in human MSCs and might also act as a key molecule determining MSC proliferation and differentiation. © AlphaMed Press 2014."
}