Triggering neural differentiation of ES cells by subtype switching of importin-alpha.
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.
Yasuhara
Noriko
N
Department of Cell Biology and Neuroscience, Graduate School of Medicine, Osaka University, 2-2 Yamada-oka, Suita, Osaka 565-0871, Japan.
Shibazaki
Noriko
N
Tanaka
Shinya
S
Nagai
Masahiro
M
Kamikawa
Yasunao
Y
Oe
Souichi
S
Asally
Munehiro
M
Kamachi
Yusuke
Y
Kondoh
Hisato
H
Yoneda
Yoshihiro
Y
D021581:Active Transport, Cell Nucleus; D000595:Amino Acid Sequence; D000818:Animals; D002454:Cell Differentiation; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism*; D053595:Embryonic Stem Cells / Q000502:physiology*; D053605:Leukemia Inhibitory Factor / Q000494:pharmacology; D051379:Mice; D008954:Models, Biological; D008969:Molecular Sequence Data; D009474:Neurons / Q000502:physiology*; D017386:Sequence Homology, Amino Acid; D014157:Transcription Factors / Q000378:metabolism; D028901:alpha Karyopherins / Q000235:genetics / Q000378:metabolism*
D053605:Leukemia Inhibitory Factor; D014157:Transcription Factors; D028901:alpha Karyopherins