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Inhibition of MAGEA2 regulates pluripotency, proliferation, apoptosis, and differentiation in mouse embryonic stem cells
Author(s) -
Park Song,
Han Jee Eun,
Kim HyeonGyeom,
Kim HeeYeon,
Kim MinGi,
Park JinKyu,
Cho GilJae,
Huang Hai,
Kim Myoung Ok,
Ryoo Zae Young,
Han SeHyeon,
Choi SeongKyoon
Publication year - 2020
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.29692
Subject(s) - embryoid body , embryonic stem cell , microbiology and biotechnology , gene knockdown , biology , cellular differentiation , stem cell , rex1 , cell cycle , apoptosis , chemistry , induced pluripotent stem cell , gene , genetics
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.