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Nat Cell Biol. 2007 Jan;9(1):72-9. Epub 2006 Dec 10.

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

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  • 1Department of Cell Biology and Neuroscience, Graduate School of Medicine, Osaka University, 2-2 Yamada-oka, Suita, Osaka 565-0871, Japan.

Erratum in

  • Nat Cell Biol. 2007 Apr;9(4):479.

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.

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