PhD Research Project

Marta Shahbazi

Decoding cell fate decisions in the early human embryo

Marta Shahbazi

The first two weeks of human development transform a single-cell into a complex, bilaminar embryo. During this critical period, cells acquire distinct identies and organise into increasingly complex tissue architectures. By day 14, the human embryo contains the embryonic disc, which will generate the fetus, and a diverse set of extra-embryonic tissues that support the pregnancy. At the same time, early human development is particularly prone to chromosome segregation errors, resulting in embryos containing a mix of euploid and aneuploid cells.

What is the fate of cells in the early human embryo? This PhD project will address this fundamental question by investigating how cells acquire new identities during early human development. We will focus on:

  1. Where do the cells of the post-implantation embryo come from? We will trace the origins of key cell populations that emerge after implantation, including extra-embryonic mesoderm and primordial germ cells, the progenitors of the gametes.
  2. How plastic are cells in the early embryo? We will investigate whether cells that are initially specified towards one fate retain the ability to change their identity in response to their environmental context and define the mechanisms that regulate this plasticity.
  3. What happens to aneuploid cells? Aneuploid cells are enriched in extra-embryonic tissues while being depleted from the embryonic disc. We will track the fate of aneuploid cells to determine how different tissues tolerate or eliminate chromosome abnormalities.

To address these questions, we will culture human embryos up to day 14 and analyse them using single-cell genomic approaches and advanced imaging. The project will be carried out in collaboration with Roser Vento-Tormo at the Wellcome Sanger Institute, who will co-supervise the project. This multidisciplinary project will combine human embryology, developmental biology, genomics and quantitative imaging to uncover how cell fate is established during a critical developmental window.

Relevant Reading

A blastocyst-derived in vitro model of the human chorionSchwarz LC, Shannon MJ, McNeill G, Sakata RC, Rosa VS, Cheah K, Keller L, Snell P, Christie L, Elder K, Mania A, Weavers L, Gibbons R, Budak TP, Sarris I, Barrie A, Campbell A, Vento-Tormo R, Smith GD, Beristain AG, Shahbazi MNbioRxiv: (2025) preprint
Early human development and stem cell-based human embryo modelsShahbazi MN, Pasque VCell Stem Cell 31(10): 1398-1418 (2024)
Self-organization of the human embryo in the absence of maternal tissuesShahbazi MN, Jedrusik A, Vuoristo S, Recher G, Hupalowska A, Bolton V, Fogarty NME, Campbell A, Devito LG, Ilic D, Khalaf Y, Niakan KK, Fishel S, Zernicka-Goetz MNature Cell Biology 18(6): 700-708 (2016)

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