AIRE is a critical spindle-associated protein in embryonic stem cells

  1. Bin Gu
  2. Jean-Philippe Lambert
  3. Katie Cockburn
  4. Anne-Claude Gingras
  5. Janet Rossant  Is a corresponding author
  1. Hospital for Sick Children, Canada
  2. 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.

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Article and author information

Author details

  1. Bin Gu

    Program in Developmental and Stem Cell Biology, Hospital for Sick Children, Toronto, Canada
    Competing interests
    The authors declare that no competing interests exist.
  2. Jean-Philippe Lambert

    Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Canada
    Competing interests
    The authors declare that no competing interests exist.
  3. Katie Cockburn

    Program in Developmental and Stem Cell Biology, Hospital for Sick Children, Toronto, Canada
    Competing interests
    The authors declare that no competing interests exist.
  4. Anne-Claude Gingras

    Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Canada
    Competing interests
    The authors declare that no competing interests exist.
  5. Janet Rossant

    Program in Developmental and Stem Cell Biology, Hospital for Sick Children, Toronto, Canada
    For correspondence
    janet.rossant@sickkids.ca
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-3731-5466

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.

Reviewing Editor

  1. Martin Pera, University of Melbourne, Australia

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).

Version history

  1. Received: April 26, 2017
  2. Accepted: July 17, 2017
  3. Accepted Manuscript published: July 25, 2017 (version 1)
  4. Version of Record published: August 17, 2017 (version 2)

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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  1. Bin Gu
  2. Jean-Philippe Lambert
  3. Katie Cockburn
  4. Anne-Claude Gingras
  5. Janet Rossant
(2017)
AIRE is a critical spindle-associated protein in embryonic stem cells
eLife 6:e28131.
https://doi.org/10.7554/eLife.28131

Share this article

https://doi.org/10.7554/eLife.28131

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