Triggering neural differentiation of ES cells by subtype switching of importin-α
Triggering neural differentiation of ES cells by subtype switching of importin-α
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DOI：
10.1038/ncb1521
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发表时间：
2007-01-01
影响因子：
21.3
通讯作者：
Yoneda, Yoshihiro
中科院分区：
文献类型：
--
作者：
Yasuhara, Noriko;Shibazaki, Noriko;Yoneda, Yoshihiro
核蛋白通过转运因子如importin- α和importin- β选择性导入细胞核（1,2）。本研究表明，在小鼠胚胎干细胞（ES）的神经分化过程中，importin-alpha亚型的表达受到严格调控，并且importin-alpha亚型表达的转换对神经分化至关重要。此外，在白血病抑制因子（LIF）和血清存在的情况下，在未分化的ES细胞中再现importin-alpha亚型表达的转换诱导了神经分化，并与参与ES-神经身份确定的Oct3/4、Brn2和SOX2的调控表达相协调。这些转录因子被特定亚型的importin- α选择性地导入细胞核。因此，importin-alpha亚型转换通过调节一组特定转录因子的核输入对细胞分化有重要影响。这是第一个提出运输因子应该被认为是决定细胞命运的主要因素的研究。
Nuclear proteins are selectively imported into the nucleus by transport factors such as importin-alpha and importin-beta(1,2). Here, we show that the expression of importin-alpha subtypes is strictly regulated during neural differentiation of mouse embryonic stem (ES) cells, and that the switching of importin-alpha subtype expression is critical for neural differentiation. Moreover, reproducing the switching of importin-alpha subtype expression in undifferentiated ES cells induced neural differentiation in the presence of leukaemia inhibitory factor (LIF) and serum, coordinated with the regulated expression of Oct3/4, Brn2 and SOX2, which are involved in ES-neural identity determination. These transcription factors were selectively imported into the nucleus by specific subtypes of importin-alpha. Thus, importin-alpha subtype switching has a major impact on cell differentiation through the regulated nuclear import of a specific set of transcription factors. This is the first study to propose that transport factors should be considered as major players in cell-fate determination.