Pluripotent cell identity in 3D
Mouse and human embryos undergo a global transformation as they implant in the maternal uterus. This transformation is fundamental for developmental progression and entails concomitant changes in tissue shape and stem cell identity. We have recently shown that the transformation of embryonic cells into an epithelial tissue is controlled by the pluripotency gene regulatory network. Our current research is aimed at dissecting how the acquisition of epithelial features regulates pluripotent cell identity and fate. This will help us understand the basic principles that govern self-organisation during development.
Selected publications:
Orietti, L. C. et al. Embryo Size Regulates the Timing and Mechanism of Pluripotent Tissue Morphogenesis. Stem Cell Reports, doi:10.1016/j.stemcr.2020.09.004 (2020).
Shahbazi, M. N., Siggia, E. D. & Zernicka-Goetz, M. Self-organization of stem cells into embryos: A window on early mammalian development. Science 364, 948-951, doi:10.1126/science.aax0164 (2019).
Shahbazi, M. N. et al. Pluripotent state transitions coordinate morphogenesis in mouse and human embryos. Nature 552, 239-243, doi:10.1038/nature24675 (2017).
Human embryo development
The development of human embryos beyond implantation remains poorly characterised due to technical and ethical difficulties. We have established conditions that allow human embryo development in vitro up to the internationally recognised day-14 limit. We now want to employ this method to study gene function during human development, and gain a mechanistic understanding of how human embryos become remodelled as they develop beyond implantation. This is a compelling approach to characterise the molecular physiology of early embryo development and identify potential mechanisms behind pregnancy loss.
This work has been approved by the HFEA and the Cambridgeshire and Hertfordshire Research Ethics Committee.
Here you can find more detailed information about our human embryo research program.
Selected publications:
Shahbazi, M. N. et al. Developmental potential of aneuploid human embryos cultured beyond implantation. Nat Commun 11, 3987, doi:10.1038/s41467-020-17764-7 (2020).
Shahbazi, M. N. Mechanisms of human embryo development: from cell fate to tissue shape and back. Development 147, doi:10.1242/dev.190629 (2020).
Shahbazi, M. N. & Zernicka-Goetz, M. Deconstructing and reconstructing the mouse and human early embryo. Nature cell biology 20, 878-887, doi:10.1038/s41556-018-0144-x (2018).
Shahbazi, M. N. et al. Self-organization of the human embryo in the absence of maternal tissues. Nat Cell Biol 18, 700-708, doi:10.1038/ncb3347 (2016).