Triggering neural differentiation of ES cells by subtype switching of importin-alpha
- PMID: 17159997
- DOI: 10.1038/ncb1521
Triggering neural differentiation of ES cells by subtype switching of importin-alpha
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.
Comment in
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Normal brain development in importin-alpha5 deficient-mice.Nat Cell Biol. 2007 Dec;9(12):1337-8; author reply 1339. doi: 10.1038/ncb1207-1337. Nat Cell Biol. 2007. PMID: 18059353 No abstract available.
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