MEST Regulates the Stemness of Human Periodontal Ligament Stem Cells
MEST Regulates the Stemness of Human Periodontal Ligament Stem Cells
复制标题
DOI：
10.1155/2020/9672673
复制
发表时间：
2020-07-08
影响因子：
4.3
通讯作者：
Maeda, Hidefumi
中科院分区：
文献类型：
--
作者：
Hasegawa, Daigaku;Hasegawa, Kana;Maeda, Hidefumi
牙周膜干细胞(PDLSCs)被认为是牙周组织再生的有用细胞来源。然而，其中一个问题是难以获得足够数量的PDLSCs用于临床应用，因为很少有PDLSCs可以从供者的PDL组织中分离出来。因此，我们的目标是确定一种将人PDL细胞转化为干细胞的特定因子。在这项研究中，通过微阵列分析比较人PDLSC系(2-14和2-23)与低分化潜能细胞系(2-52)的基因图谱，确定了印记基因中胚层特异性转录本(MEST)。Mest表达于2-23细胞的胞浆。通过siRNA在2-23细胞中敲除MEST可抑制干细胞标志物CD105、CD146、p75NTR、N-钙粘素和NANOG的表达；抑制成骨细胞、脂肪细胞和软骨细胞的增殖能力和多向分化能力。另一方面，MEST在2-52细胞中的过表达增强了干细胞标志物和PDL相关标志物的表达，增强了细胞的多向分化能力。此外，MEST过表达的2-52细胞的形态从纺锤形变为干细胞样的圆形，类似于2-14和2-23细胞的形态。这些结果表明，MEST在维持PDLSC的干性方面起着关键作用，并将PDL细胞转化为PDLSC样细胞。因此，本研究提示MEST可能是通过诱导PDLSCs促进牙周组织再生的一种治疗因素。
Periodontal ligament (PDL) stem cells (PDLSCs) have been reported as a useful cell source for periodontal tissue regeneration. However, one of the issues is the difficulty of obtaining a sufficient number of PDLSCs for clinical application because very few PDLSCs can be isolated from PDL tissue of donors. Therefore, we aimed to identify a specific factor that converts human PDL cells into stem-like cells. In this study, microarray analysis comparing the gene profiles of human PDLSC lines (2-14 and 2-23) with those of a cell line with a low differentiation potential (2-52) identified the imprinted gene mesoderm-specific transcript (MEST). MEST was expressed in the cytoplasm of 2-23 cells. Knockdown of MEST by siRNA in 2-23 cells inhibited the expression of stem cell markers, such as CD105, CD146, p75NTR, N-cadherin, and NANOG; the proliferative potential; and multidifferentiation capacity for osteoblasts, adipocytes, and chondrocytes. On the other hand, overexpression of MEST in 2-52 cells enhanced the expression of stem cell markers and PDL-related markers and the multidifferentiation capacity. In addition, MEST-overexpressing 2-52 cells exhibited a change in morphology from a spindle shape to a stem cell-like round shape that was similar to 2-14 and 2-23 cell morphologies. These results suggest that MEST plays a critical role in the maintenance of stemness in PDLSCs and converts PDL cells into PDLSC-like cells. Therefore, this study indicates that MEST may be a therapeutic factor for periodontal tissue regeneration by inducing PDLSCs.