Transcriptional regulation in early embryo development
Dr. Bin Gu
Previously, I discovered the expression of Autoimmune Regulator (AIRE), a promiscuous transcription activator previously thought to be restrictively expressed in thymic medullary epithelium cells, where it promotes immune-tolerance, in embryonic stem (ES) cells and early embryos. I uncovered two unexpected functions of AIRE specific to ES cells and early embryonic cells: 1) AIRE sustains pluripotency by promoting a permissive expression profile1,2, and 2) AIRE maintains proliferative fidelity by sustaining mitotic spindle integrity3. More recently, I developed 2C-HR-CRISPR4, which allows rapid generation of large fragment knock-in mouse models with high efficiency, in collaboration with Eszter Posfai. With these, I am now dissecting the transcriptional regulatory mechanism during crucial processes in early embryo development such as zygotic genome activation and lineage segregation, using knock-in reporter mice, live imaging, live protein perturbation, and genomics technologies.
- Gu, B.et al.Aire regulates the expression of differentiation-associated genes and self-renewal of embryonic stem cells. Biochem Biophys Res Commun 394, 418-423, doi:10.1016/j.bbrc.2010.03.042 (2010).
- Gu, B.et al.Aire promotes the self-renewal of embryonic stem cells through Lin28. Stem Cells Dev 21, 2878-2890, doi:10.1089/scd.2012.0097 (2012).
- Gu, B., Lambert, J. P., Cockburn, K., Gingras, A. C. & Rossant, J. AIRE is a critical spindle-associated protein in embryonic stem cells. Elife 6, doi:10.7554/eLife.28131 (2017).
- Gu, B., Posfai, E. & Rossant, J. Efficient generation of targeted large insertions by microinjection into two-cell-stage mouse embryos. Nat Biotechnol 36, 632-637, doi:10.1038/nbt.4166 (2018).