Integrity of the short arm of the nuclear pore Y-complex is required for mouse embryonic stem cell growth and differentiation

Many cellular processes, ranging from cell division to differentiation, are controlled by nudear pore complexes (NPCs). However, studying the contributions of individual NPC subunits to these processes in vertebrates has long been impeded by their complexity and the lack of efficient genetic tools. Here, we use genome editing in mouse embryonic stem cells (mESCs) to characterize the role of NPC structural components, focusing on the short arm of the Y-complex that comprises Nup85, Seh1 and Nup43. We show that Seh1 and Nup43, although dispensable in pluripotent mESCs, are required for their normal cell growth rates, their viability upon differentiation and for the maintenance of proper NPC density. mESCs with an N-terminally truncated Nup85 mutation (in which interaction with Seh1 is greatly impaired) feature a similar reduction of NPC density. However, their proliferation and differentiation are unaltered, indicating that it is the integrity of the Y-complex, rather than the number of NPCs, that is critical to ensure these processes.

Automated summary

This study characterizes the role of NPC structural components in cellular processes using genome editing in mouse embryonic stem cells. The findings suggest that the integrity of the Y-complex, rather than the number of NPCs, is critical for normal cell growth, differentiation, and NPC density maintenance.