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Inhibition of MAGEA2 regulates pluripotency,proliferation, apoptosis,and differentiation in mouse embryonic stem cells
Authors:Song Park  Jee Eun Han  Hyeon-Gyeom Kim  Hee-Yeon Kim  Min-Gi Kim  Jin-Kyu Park  Gil-Jae Cho  Hai Huang  Myoung Ok Kim  Zae Young Ryoo  Se-Hyeon Han  Seong-Kyoon Choi
Affiliation:1. Core Protein Resources Center, DGIST, Daegu, South Korea;2. College of Veterinary Medicine, Kyungpook National University, Daegu, South Korea;3. School of Life Science, BK21 Plus KNU Creative Bioresearch Group, Kyungpook National University, Daegu, South Korea;4. The School of Animal BT Science, Kyungpook National University, Sangju-si, Gyeongsangbuk-do, South Korea;5. School of Media Communication, Hanyang University, Seongdonggu, Seoul, South Korea
Abstract:Mouse embryonic stem cells (mESCs) exhibit self-renewal and pluripotency, can differentiate into all three germ layers, and serve as an essential model in stem cell research and for potential clinical application in regenerative medicine. Melanoma-associated antigen A2 (MAGEA2) is not expressed in normal somatic cells but rather in different types of cancer, especially in undifferentiated cells, such as in the testis, differentiating cells, and ESCs. However, the role of MAGEA2 in mESCs remains to be clarified. Accordingly, in this study, we examined the expression and functions of MAGEA2 in mESCs. MAGEA2 messenger RNA (mRNA) expression was decreased during mESCs differentiation. MAGEA2 function was then evaluated in knockdown mESC. MAGEA2 knockdown resulted in decreased pluripotency marker gene expression in mESCs consequent to increased Erk1/2 phosphorylation. Decreased MAGEA2 expression inhibited mESC proliferation via S phase cell cycle arrest with a subsequent decrease in cell cycle-associated genes Cdk1, Cdk2, Cyclin A1, Cyclin D1, and Cdc25a. Apoptotic mESCs markedly increased along with cleaved forms of caspases 3, 6, and 7 and PARP expression, confirming caspase-dependent apoptosis. MAGEA2 knockdown significantly decreased embryoid body size in vitro when cells were differentiated naturally and teratoma size in vivo, concomitant with decreased ectoderm marker gene expression. These findings suggested that MAGEA2 regulates ESC pluripotency, proliferation, cell cycle, apoptosis, and differentiation. The enhanced understanding of the regulatory mechanisms underlying diverse mESC characteristics will facilitate the clinical application of mESCs.
Keywords:apoptosis  differentiation  MAGEA2  pluripotency  proliferation
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