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Over the past decades, a lot of effort has been put into elucidating the molecular pathways controlling the first lineage segregations in the mammalian preimplantation embryo. Due to its great accessibility and simplicity, the mouse model was the one that was most explored. However, as recent studies have shown, there might exist essential differences during early development between the mouse and other mammalians species like the human. Based on what was learned from the mouse model and building up on our recently published single-cell transcriptomic roadmap of the early human embryo, we aim to investigate which molecular pathways control the first lineage segregations in the human preimplantation embryo with a special emphasis in the potential role of Hippo pathway during trophectoderm-inner cell mass segregation. For that purpose, we will make use of state-of-the-art gene editing techniques in both human embryonic stem cells and early human embryo to interfere with selected molecular players and test their implications by studying the lineage commitment of edited cells and any downstream transcriptional effects in developing human embryos.


My PhD studies include also a more translational strand, that aims to bring the human embryonic stem cell (hESC)-derived treatments to the clinic. Aiming to find a successful replacement therapy for Age-related Macular Degeneration, in our lab we are working on the production of clinical grade hESC-derived retinal pigmented epithelium (RPE) cells. My contributions to the big picture include the establishment of a xeno-free and defined hESC-RPE differentiation protocol, the identification of relevant cell surface markers that could help in the purification or quality control, and the establishment of routines for the cGMP production of these cells.



Comprehensive Cell Surface Protein Profiling Identifies Specific Markers of Human Naive and Primed Pluripotent States
Collier Aj, Panula Sp, Schell Jp, Chovanec P, Plaza Reyes A, Petropoulos S, et al
Cell stem cell 2017;20(6):874-890.e7

Towards a CRISPR view of early human development: applications, limitations and ethical concerns of genome editing in human embryos
Plaza Reyes A, Lanner F
Development (Cambridge, England) 2017;144(1):3-7

Single-Cell RNA-Seq Reveals Lineage and X Chromosome Dynamics in Human Preimplantation Embryos
Petropoulos S, Edsgärd D, Reinius B, Deng Q, Panula Sp, Codeluppi S, et al
Cell 2016;165(4):1012-26

The human PRD-like homeobox gene LEUTX has a central role in embryo genome activation
Jouhilahti Em, Madissoon E, Vesterlund L, Töhönen V, Krjutškov K, Plaza Reyes A, et al
Development (Cambridge, England) 2016;143(19):3459-3469

Xeno-Free and Defined Human Embryonic Stem Cell-Derived Retinal Pigment Epithelial Cells Functionally Integrate in a Large-Eyed Preclinical Model
Plaza Reyes A, Petrus-reurer S, Antonsson L, Stenfelt S, Bartuma H, Panula S, et al
Stem cell reports 2016;6(1):9-17