First Author | Gu B | Year | 2017 |
Journal | Elife | Volume | 6 |
PubMed ID | 28742026 | Mgi Jnum | J:242967 |
Mgi Id | MGI:5907277 | Doi | 10.7554/eLife.28131 |
Citation | Gu B, et al. (2017) AIRE is a critical spindle-associated protein in embryonic stem cells. Elife 6:e28131 |
abstractText | 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. |