摘要
Abstract
The Melanoma-associated Antigen gene family (MAGE) generally encodes for tumour antigens. We had identified that one of the MAGE gene members, Mageb16 was highly expressed in undifferentiated murine embryonic stem cells (ESCs). While the role of Mageb16 in stemness and differentiation of pluripotent stem cells is completely unknown, here, in our current study, we have demonstrated that Mageb16 (41 kDa) is distributed in cytosol and/or in surface membrane in undifferentiated ESCs. A transcriptome study performed at differentiated short hairpin RNA (shRNA)-mediated Mageb16 knockdown (KD) ESCs and scrambled control (SCR) ESCs until a period of 22 days, revealed that Mageb16 KD ESCs mainly differentiated towards cells expressing mesodermal and cardiovascular lineage - gene markers. Gene markers of other mesoderm-oriented biological processes such as adipogenesis, osteogenesis, limb morphogenesis and spermatogenesis were also significantly enriched in the differentiated Mageb16 KD ESCs. The expression levels of contractile genes were higher in differentiated Mageb16 KD ESCs when compared to differentiated SCR and wild ESCs, suggesting a higher cardiomyogenic potential of Mageb16 depleted ESCs. Further analysis indicates that regulative epigenetic networks and nucleocytoplasmic modifications induced by the depletion of Mageb16, may play a probable role in differentiation.
摘要译文
摘要黑色素瘤相关抗原基因家族（MAGE）通常编码肿瘤抗原。我们确定了一个MAGE基因成员，Mageb16在未分化的小鼠胚胎干细胞（ESCs）中高表达。虽然Mageb16在多能干细胞的干细胞和分化中的作用尚不清楚，但在此，在我们目前的研究中，我们已经证明Mageb16（41kDa）分布在未分化的ESC中的胞质溶胶和/或表面膜中。转化组研究在分化的短发夹RNA（shRNA）介导的Mageb16敲低（KD）胚胎干细胞和乱序对照（SCR）胚胎干细胞中进行，直至22天，显示Mageb16 KD胚胎干细胞主要分化为表达中胚层和心血管谱系的细胞 - 基因标记。其他中胚层导向生物过程的基因标记，如脂肪生成，成骨，肢体形态发生和精子发生也在分化的Mageb16 KD ESC中显着富集。与分化的SCR和野生型ESC相比，分化的Mageb16 KD胚胎干细胞中收缩基因的表达水平更高，表明Mageb16耗尽的胚胎干细胞具有更高的心肌形成潜力。进一步分析表明，由Mageb16耗尽诱导的调节表观遗传网络和核质转化可能在分化中起到可能的作用。
John Antonydas Gaspar[1];Sureshkumar Perumal Srinivasan;Poornima Sureshkumar[1];Michael Xavier Doss[1];Jürgen Hescheler[1];Symeon Papadopoulos[2];Agapios Sachinidis[1]. Depletion of Mageb16 induces differentiation of pluripotent stem cells predominantly into mesodermal derivatives[J]. Scientific reports, 2017