Identification and functional comparison of Bcl2 splicing isoforms in mouse embryonic stem cells
Identification and functional comparison of Bcl2 splicing isoforms in mouse embryonic stem cells
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小鼠胚胎干细胞Bcl2剪接异构体的鉴定及功能比较
DOI：
10.1016/j.bbrc.2020.01.140
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发表时间：
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通讯作者：
Jian Rui
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作者：
Wang Xueyue;Wang Jiaqi;Cheng Yuda;Wang Jiali;Tian Yanping;Zhang Junlei;Xiong Jiaxiang;Yang Yi;Wu Wei;He Ping;Liu Gaoke;Xu Yixiao;Liu Lianlian;Ren Bangqi;Ruan Yan;Jian Rui
胚胎干细胞（ESCs）是研究发育过程的理想模型，也是开发再生医学的重要来源。利用细胞凋亡促进胚胎发生期间信号事件的准确重演，并允许ESC在分化期间有效扩增。bcl 2是内源性抗凋亡通路的关键调节因子，编码两种剪接异构体。然而，Bcl 2剪接异构体在小鼠胚胎干细胞（mESCs）的鉴定和功能比较仍有待阐明。在这里，我们提供的证据表明，这两个Bcl 2剪接变异体表达的胚胎干细胞。尽管结构不同，但它们具有相似的亚细胞定位。Bcl 2 α和Bcl 2 β均能增强ESCs的分化效率，有效提高ESCs在无血清条件下的存活和生长。但Bcl 2 α的功能作用强于Bcl 2 β。只有Bcl 2 α能维持无血清培养的ESCs的长期扩增和多能性。综上所述，我们的研究结果证明了以前未知的功能差异Bcl 2选择性剪接异构体在胚胎干细胞，并奠定了基础，为未来的努力工程胚胎干细胞再生医学。
Embryonic stem cells (ESCs) provide an ideal model for investigating developmental processes and are great sources for developing regenerative medicine. Harnessing apoptosis facilitates accurate recapitulation of signalling events during embryogenesis and allows efficient expansion of the ESCs during differentiation. Bcl2, a key regulator of intrinsic anti-apoptotic pathway, encodes two splicing isoforms. However, the identification and functional comparison of Bcl2 splicing isoforms in mouse ESCs (mESCs) remains to be elucidated. Here, we provide the evidence that both Bcl2 splicing variants are expressed in mESCs. Despite the structural difference, they have similar subcellular localisation. Both Bcl2α and Bcl2β enhance differentiation efficiency of the ESCs and effectively improve the survival and growth of ESCs under serum-free conditions. However, the functional effect of Bcl2α was more potent than that of Bcl2β. Moreover, only Bcl2α could maintain the long-term expansion and pluripotency of ESCs cultured in serum-free medium. Taken together, our results demonstrate previously unknown functional differences in Bcl2 alternative splicing isoforms in ESCs, and lay the foundation for future efforts to engineer ESCs for regenerative medicine.