AIRE is a critical spindle-associated protein in embryonic stem cells
- Hospital for Sick Children, Canada
- Mount Sinai Hospital, Canada
Abstract
Embryonic stem (ES) cells go though embryo-like cell cycles regulated by specialized molecular mechanisms. However, it is not known whether there are ES cell-specific mechanisms regulating mitotic fidelity. Here we showed that Autoimmune Regulator (Aire), a transcription coordinator involved in immune tolerance processes, is a critical spindle-associated protein in mouse ES(mES) cells. BioID analysis showed that AIRE associates with spindle-associated proteins in mES cells. Loss of function analysis revealed that Aire was important for centrosome number regulation and spindle pole integrity specifically in mES cells. We also identified the c-terminal LESLL motif as a critical motif for AIRE's mitotic function. Combined maternal and zygotic knockout further revealed Aire's critical functions for spindle assembly in preimplantation embryos. These results uncovered a previously unappreciated function for Aire and provide new insights into the biology of stem cell proliferation and potential new angles to understand fertility defects in humans carrying Aire mutations.
Data availability
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AIRE BioID datasetPublicly available at ProteomeXchange (accession no. PXD005529).
Article and author information
Author details
Funding
Canadian Institutes of Health Research (FDN-143334)
- Bin Gu
- Katie Cockburn
- Janet Rossant
Ontario Institute for Regenerative Medicine
- Bin Gu
Cancer Research Society
- Jean-Philippe Lambert
Canadian Institutes of Health Research (FDN143301)
- Jean-Philippe Lambert
- Anne-Claude Gingras
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: All animal work was carried out following Canadian Council on Animal Care Guidelines for Use of Animals in Research and Laboratory Animal Care under protocols approved by The Centre for Phenogenomics Animal Care Committee (protocol number: 20-0026H).
Copyright
© 2017, Gu et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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AIRE is a critical spindle-associated protein in embryonic stem cells
eLife 6:e28131.
https://doi.org/10.7554/eLife.28131
