Graduate School of Frontier Biosciences, Osaka University

Japanese

Triggering neural differentiation of ES cells by subtype switching of importin-α.

Journal Nat Cell Biol 9, 72-76 (2007)
Authors Noriko Yasuhara, Noriko Shibazaki, Shinya Tanaka, Masahiro Nagai, Yasunao Kamikawa, Souichi Oe, Munehiro Asally, Yusuke Kamachi, Hisato Kondoh and Yoshihiro Yoneda
Title Triggering neural differentiation of ES cells by subtype switching of importin-α.
PubMed 17159997
Abstract Nuclear proteins are selectively imported into the nucleus by transport factors such as importin-alpha and importin-beta. 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.