title: Sox2 suppression by miR-21 governs human mesenchymal stem cell properties.
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 round-shaped (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 of MSCs 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 BM-MSCs compared with SS-AF-MSCs. We further demonstrated for the first time a direct interaction between miR-21 and the pluripotency marker 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 BM-MSCs, 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.
authors.affiliation: Laboratory of Biology, School of Medicine, University of Athens, Athens, Greece; Cell and Gene Therapy Laboratory, Center of Basic Research II, and Biotechnology Laboratory, Center of Basic Research, Biomedical Research Foundation of the Academy of Athens, Athens, Greece; First Department of Obstetrics and Gynecology, School of Medicine, University of Athens, Athens, Greece.
authors.forename: Ourania
authors.initials: O
authors.lastname: Trohatou
authors.forename: Dimitra
authors.initials: D
authors.lastname: Zagoura
authors.forename: Vasiliki
authors.initials: V
authors.lastname: Bitsika
authors.forename: Kalliopi I
authors.initials: KI
authors.lastname: Pappa
authors.forename: Aristidis
authors.initials: A
authors.lastname: Antsaklis
authors.forename: Nicholas P
authors.initials: NP
authors.lastname: Anagnou
authors.forename: Maria G
authors.initials: MG
authors.lastname: Roubelakis
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D001854:Bone Marrow Cells / Q000166:cytology / Q000502:physiology; D002454:Cell Differentiation / Q000502:physiology; D049109:Cell Proliferation; D002478:Cells, Cultured; D018398:Homeodomain Proteins / Q000235:genetics; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000502:physiology*; D035683:MicroRNAs / Q000378:metabolism*; D039902:Multipotent Stem Cells / Q000166:cytology / Q000502:physiology; D000071317:Nanog Homeobox Protein; D050814:Octamer Transcription Factor-3 / Q000235:genetics; D055748:SOXB1 Transcription Factors / Q000235:genetics* / Q000378:metabolism*; D059467:Transcriptome
chemical_list: D020413:3' Untranslated Regions; D018398:Homeodomain Proteins; C524940:MIRN21 microRNA, human; D035683:MicroRNAs; C486780:NANOG protein, human; D000071317:Nanog Homeobox Protein; D050814:Octamer Transcription Factor-3; C494173:POU5F1 protein, human; C527782:SOX2 protein, human; D055748:SOXB1 Transcription Factors
keywords: Amniotic fluid mesenchymal stem cells; Bone marrow mesenchymal stem cells; Cell cycle; Sox2; Umbilical cord blood mesenchymal stem cells; miR-21