The role of Importin-βs in the maintenance and lineage commitment of mouse embryonic stem cells
| Autor: | Yoshihiro Yoneda, Percival Sangel, Masahiro Oka |
|---|---|
| Jazyk: | angličtina |
| Předmět: |
Homeobox protein NANOG
NPC nuclear pore complex ESC Importin Germ layer Biology environment and public health Article General Biochemistry Genetics and Molecular Biology SOX2 mESCs mouse embryonic stem cells RA retinoic acid lcsh:QH301-705.5 Genetics Gene knockdown Neuroectoderm NES nuclear export signals ME mesoendoderm MEF mouse embryonic fibroblast NLS nuclear localization signals Embryonic stem cell Cell biology lcsh:Biology (General) Differentiation embryonic structures Germ layers Exportin Nuclear localization sequence NE neural ectoderm |
| Zdroj: | FEBS Open Bio, Vol 4, Iss C, Pp 112-120 (2014) FEBS Open Bio |
| ISSN: | 2211-5463 |
| DOI: | 10.1016/j.fob.2014.01.001 |
| Popis: | Members of the Importin-β family recognize nuclear localization signals (NLS) and nuclear export signals (NES). These proteins play important roles in various nucleocytoplasmic transport processes in cells. Here, we examined the expression patterns of 21 identified Importin-β genes in mouse embryonic stem cells (mESCs), mouse embryonic fibroblast (MEF) and mESCs differentiated into neural ectoderm (NE) or mesoendoderm (ME). We observed striking differences in the Importin-β mRNA expression levels within these cell types. We also found that knockdown of selected Importin-β genes led to suppression of Nanog, and altered the balance of Oct4/Sox2 expression ratio, which is important for NE/ME lineage choice. Furthermore, we demonstrated that knockdown of XPO4, RanBP17, RanBP16, or IPO7 differentially affected the lineage selection of differentiating mESCs. More specifically, knockdown of XPO4 selectively stimulated the mESC differentiation towards definitive endoderm, while concomitantly inhibiting NE differentiation. RanBP17 knockdown also promoted endodermal differentiation with no effect on NE differentiation. RanBP16 knockdown caused differentiation into ME, while IPO7 knockdown inhibited NE differentiation, without obvious effects on the other lineages. Collectively, our results suggest that Importin-βs play important roles in cell fate determination processes of mESCs, such as in the maintenance of pluripotency or selection of lineage during differentiation. Highlights • Importin-β expression patterns are distinct in mESCs, MEFs, NE and ME cells. • Importin-β may modulate differentiation and lineage selection in mESCs. • Suppression of either XPO4 or RanBP17 induces endodermal differentiation in mESCs. • RanBP16 suppression induces a ME differentiation in mESCs. • XPO4 and IPO7 are essential for mESC differentiation into NE cells. |
| Databáze: | OpenAIRE |
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