Park Song, Sung Yonghun, Jeong Jain, Choi Minjee, Lee Jinhee, Kwon Wookbong, Jang Soyoung, Park Si Jun, Kim Jae Young, Kim Sung Hyun, Yoon Duhak, Ryoo Zae Young, Kim Myoung Ok
School of Life Science, BK21 plus KNU Creative Bio Research Group, College of Natural Sciences, Kyungpook National University, Daegu, Republic of Korea.
Core Protein Resources Center, Daegu Gyeongbuk Institute of Science and Technology (DGIST), Daegu, Republic of Korea.
Cell Biochem Funct. 2017 Oct;35(7):392-400. doi: 10.1002/cbf.3286. Epub 2017 Sep 11.
Induced pluripotent stem (iPS) cells are important for clinical application and stem cell research. Although human melanoma-associated antigen A2 (hMAGEA2) expression is known to affect differentiation in embryonic stem cells, its specific role in iPS cells remains unclear. To evaluate the function of hMAGEA2 and its characteristics in iPS cells, we produced hMAGEA2-overexpressing iPS cells from hMAGEA2-overexpressing transgenic mice. Although the iPS cells with overexpressed hMAGEA2 did not differ in morphology, their pluripotency, and self-renewal related genes (Nanog, Oct3/4, Sox2, and Stat3), expression level was significantly upregulated. Moreover, hMAGEA2 contributed to the promotion of cell cycle progression, thereby accelerating cell proliferation. Through embryoid body formation in vitro and teratoma formation in vivo, we demonstrated that hMAGEA2 critically decreases the differentiation ability of iPS cells. These data indicate that hMAGEA2 intensifies the self-renewal, pluripotency, and degree of proliferation of iPS cells, while significantly repressing their differentiation efficiency. Therefore, our findings prove that hMAGEA2 plays key roles in iPS cells.
诱导多能干细胞（iPS细胞）对于临床应用和干细胞研究具有重要意义。虽然已知人类黑色素瘤相关抗原A2（hMAGEA2）的表达会影响胚胎干细胞的分化，但其在iPS细胞中的具体作用仍不清楚。为了评估hMAGEA2在iPS细胞中的功能及其特性，我们从过表达hMAGEA2的转基因小鼠中制备了过表达hMAGEA2的iPS细胞。虽然过表达hMAGEA2的iPS细胞在形态、多能性以及自我更新相关基因（Nanog、Oct3/4、Sox2和Stat3）方面没有差异，但其表达水平显著上调。此外，hMAGEA2有助于促进细胞周期进程，从而加速细胞增殖。通过体外形成胚状体和体内形成畸胎瘤，我们证明hMAGEA2严重降低了iPS细胞的分化能力。这些数据表明，hMAGEA2增强了iPS细胞的自我更新、多能性和增殖程度，同时显著抑制其分化效率。因此，我们的研究结果证明hMAGEA2在iPS细胞中发挥关键作用。
