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

Elife. 2017 Jul 25;6:e28131. doi: 10.7554/eLife.28131.

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.

Keywords: Aire; developmental biology; early embryo; embryonic stem cells; mouse; stem cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Division*
  • Embryonic Stem Cells / physiology*
  • Gene Knockout Techniques
  • Mice
  • Mouse Embryonic Stem Cells / physiology*
  • Protein Binding
  • Spindle Apparatus / metabolism*
  • Transcription Factors / metabolism*

Substances

  • APECED protein
  • Transcription Factors