Sox2 Suppression by miR‐21 Governs Human Mesenchymal Stem Cell Properties
Sox2 Suppression by miR‐21 Governs Human Mesenchymal Stem Cell Properties
复制标题
DOI：
10.5966/sctm.2013-0081
复制
发表时间：
2014-01
影响因子：
6
通讯作者：
Ourania Trohatou;D. Zagoura;V. Bitsika;K. Pappa;A. Antsaklis;N. Anagnou;M. Roubelakis
中科院分区：
文献类型：
--
作者：
Ourania Trohatou;D. Zagoura;V. Bitsika;K. Pappa;A. Antsaklis;N. Anagnou;M. Roubelakis
MicroRNAs （miRNAs）最近被证明是维持干细胞和决定成人和胎儿干细胞（如人间充质干细胞（hMSCs））命运的调节信号。骨髓间充质干细胞是一种多能干细胞，可以在培养中容易扩增，并且能够分化成许多谱系。我们从羊水（AF）中分离出两种胎儿间充质干细胞（MSCs）亚群，即纺锤形（SS）和圆形（RS）细胞，并根据它们的表型、多能性、增殖率和分化潜力对它们进行了表征。在这项研究中，我们分析了来自AF、骨髓（BM）和脐带血（UCB）的MSCs的miRNA谱。我们最初鉴定了67种不同的mirna，它们在所有三种类型的MSCs中表达，但表达水平不同，取决于来源。一项更详细的分析显示，与SS - AF - MSCs相比，miR - 21在RS - AF - MSCs和BM - MSCs中的表达水平更高。我们进一步首次证明了miR - 21与多能性标记物Sox2之间的直接相互作用。miR - 21的诱导强烈抑制了Sox2在SS - AF - MSCs中的表达，导致克隆和增殖潜能降低以及细胞周期阻滞。引人注目的是，在RS - AF - MSCs和BM - MSCs中观察到miR - 21抑制的相反效果，导致增殖率增强。最后，miR - 21诱导加速了SS - AF - MSCs的成骨和受损的脂肪生成和软骨生成。因此，这些发现表明miR - 21可能通过调节人类间充质干细胞中Sox2的表达特异性发挥作用，也可能作为决定间充质干细胞增殖和分化的关键分子。
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.