Critical roles of hMAGEA2 in induced pluripotent stem cell pluripotency, proliferation, and differentiation

Abstract

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.

Inhibition of MAGEA2 regulates pluripotency, proliferation, apoptosis, and differentiation in mouse embryonic stem cells

“…Our predictions, however, suggest that the MAGEA gene family colocalizes with ectoderm markers Pax6 and BIII-tubulin genes during early development, and are expected to interact with Pax6 and BIII-tubulin, thus affecting the ectoderm rather than the mesoderm and endoderm. 38 Furthermore, we previously reported the association between MAGEA2 and induced pluripotent stem cells (iPS), 39 showing that MAGEA2 overexpression enhances the pluripotency of iPS cells, increases proliferation, and decreases their differentiation capacity. Although our results were consistent with the reduction of pluripotency and proliferation owing to MAGEA2 downregulation, as reported herein, it seems contradictory that the differentiation ability is decreased upon both overexpression and knockdown of MAGEA2.…”

Expression dynamics of Mage family genes during self-renewal and differentiation of mouse pluripotent stem and teratocarcinoma cells

“…Thus, difference in the expression levels of Mage-a2 detected in this work between mouse pluripotent and teratocarcinoma cells, likewise in MAGE-A2 expression between human ESCs and ECCs [34], may be characteristic for teratocarcinoma cells and contribute to their malignant phenotype with imbalance of proliferation and differentiation potentials. Additionally, the over-expression of MAGEA2 was found to intensify the self-renewal and to repress differentiation efficiency of human induced pluripotent stem cells while depletion of Mageb16 in mouse ESCs induced more effective differentiation [49, 50]. In cancer cells, MAGEA2 and MAGEA6 promote cell growth and survival by targeting tumor suppressor protein AMP-activated protein kinase and preventing of ubiquitination and proteasome-dependent degradation, and acetylating p53 through histone deacetylase recruitment [6, 51–54].…”