Biomedicine Discovery Institute, Monash University, Clayton 3168, Australia.
Monash Institute of Pharmaceutical Sciences, Monash University, Parkville 3052, Australia.
Cells. 2022 Jun 12;11(12):1904. doi: 10.3390/cells11121904.
Molecular transport between the nucleus and cytoplasm of the cell is mediated by the importin superfamily of transport receptors, of which the bidirectional transporter Importin 13 (IPO13) is a unique member, with a critical role in early embryonic development through nuclear transport of key regulators, such as transcription factors Pax6, Pax3, and ARX. Here, we examined the role of IPO13 in neuronal differentiation for the first time, using a mouse embryonic stem cell (ESC) model and a monolayer-based differentiation protocol to compare IPO13 to wild type ESCs. Although IPO13 ESCs differentiated into neural progenitor cells, as indicated by the expression of dorsal forebrain progenitor markers, reduced expression of progenitor markers and compared to IPO13 was evident, concomitant with reduced nuclear localisation/transcriptional function of IPO13 import cargo Pax6. Differentiation of IPO13 cells into neurons appeared to be strongly impaired, as evidenced by altered morphology, reduced expression of key neuronal markers, and altered response to the neurotransmitter glutamate. Our findings establish that IPO13 has a key role in ESC neuronal differentiation, in part through the nuclear transport of Pax6.
细胞的核质间分子转运是由输入蛋白超家族转运受体介导的，其中双向转运蛋白 Importin 13（IPO13）是一个独特的成员，通过核转运关键调节因子（如转录因子 Pax6、Pax3 和 ARX）在早期胚胎发育中发挥关键作用。在这里，我们首次使用小鼠胚胎干细胞（ESC）模型和基于单层的分化方案，研究了 IPO13 在神经元分化中的作用，以将其与野生型 ESC 进行比较。尽管 IPO13 ESC 分化为神经祖细胞，如背侧前脑祖细胞标记物的表达所表明的，但与 IPO13 相比，祖细胞标记物 和 的表达明显减少，同时 IPO13 进口货物 Pax6 的核定位/转录功能也降低。IPO13 细胞向神经元的分化似乎受到严重损害，这表现在形态改变、关键神经元标记物表达减少以及对神经递质谷氨酸的反应改变。我们的研究结果表明，IPO13 在 ESC 神经元分化中具有关键作用，部分原因是通过核转运 Pax6。
