Biotherapeutics Translational Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), 125 Gwahak-ro, Yuseong-gu, Daejeon 34141, Korea; Department of Biomolecular Science, KRIBB School of Bioscience, Korea University of Science and Technology (UST), 217 Gajeong-ro, Yuseong-gu, Daejeon 34141, Korea.
Biotherapeutics Translational Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), 125 Gwahak-ro, Yuseong-gu, Daejeon 34141, Korea.
Stem Cell Reports. 2018 Jul 10;11(1):115-127. doi: 10.1016/j.stemcr.2018.05.009. Epub 2018 Jun 14.
Pluripotent stem cells (PSCs) represent the most promising clinical source for regenerative medicine. However, given the cellular heterogeneity within cultivation and safety concerns, the development of specific and efficient tools to isolate a pure population and eliminate all residual undifferentiated PSCs from differentiated derivatives is a prerequisite for clinical applications. In this study, we raised a monoclonal antibody and identified its target antigen as desmoglein-2 (DSG2). DSG2 co-localized with human PSC (hPSC)-specific cell surface markers, and its expression was rapidly downregulated upon differentiation. The depletion of DSG2 markedly decreased hPSC proliferation and pluripotency marker expression. In addition, DSG2-negative population in hPSCs exhibited a notable suppression in embryonic body and teratoma formation. The actions of DSG2 in regulating the self-renewal and pluripotency of hPSCs were predominantly exerted through the regulation of β-catenin/Slug-mediated epithelial-to-mesenchymal transition. Our results demonstrate that DSG2 is a valuable PSC surface marker that is essential for the maintenance of PSC self-renewal.
多能干细胞（PSCs）代表了再生医学最有前途的临床来源。然而，鉴于培养过程中的细胞异质性和安全问题，开发特定且有效的工具来分离纯细胞群并消除分化衍生物中所有残留的未分化 PSCs，是临床应用的前提条件。在这项研究中，我们制备了一种单克隆抗体，并鉴定其靶抗原为桥粒芯糖蛋白-2（DSG2）。DSG2 与人类 PSC（hPSC）特异性细胞表面标志物共定位，其表达在分化时迅速下调。DSG2 的耗竭显著降低了 hPSC 的增殖和多能性标志物表达。此外，hPSC 中的 DSG2 阴性群体在胚胎体和畸胎瘤形成方面表现出明显的抑制。DSG2 通过调节β-连环蛋白/Slug 介导的上皮-间充质转化来调节 hPSC 的自我更新和多能性。我们的研究结果表明，DSG2 是一种有价值的 PSC 表面标志物，对于维持 PSC 的自我更新至关重要。
