This fundamental research project is focussed on early human embryogenesis. These studies are unique because research on human embryos is only allowed in a few countries worldwide including Belgium (regulated by the law of May 2003). The Centre for Reproductive Medicine (CRG, UZ Brussel) provides embryos for research, in particular good quality embryos affected with a genetic disease after preimplantation genetic diagnosis.
We aim to investigate the embryonic states of totipotency (Cauffman et al. 2005a; Cauffman et al. 2005b; Cauffman et al. 2006; Cauffman et al. 2009; Verloes et al. 2011), pluripotency and early differentiation. We demonstrated that human embryonic cells (blastomeres) are flexible (undifferentiated) and have the same potential until the full blastocyst stage (Van de Velde et al. 2008; Geens et al; 2009; De Paepe et al. 2013), but it is not known how the blastomeres remain undifferentiated nor how they differentiate into a certain lineage. In particular, we identified new markers for totipotency in human embryos and embryonic stem cells (hESC) (Krivega et al. 2014; Krivega et al. 2015b). Data from hESC cultures and animal models showed that lineage direction is controlled by cell polarisation, cell position, cell-cell contact, the cell cycle, transcription factors, epigenetic modifications and signalling pathways (reviewed by us in De Paepe and Krivega et al. 2014). Studies on human embryos are mainly descriptive; therefore we started to perform in vitro functional studies which would greatly contribute to a better understanding of the key signals that regulate differentiation during human preimplantation development. We investigated FGF (Kuijk et al. 2012) and WNT (Krivega et al. 2015a). Understanding the pathways involved in early embryogenesis may help us to regulate development in vitro by supplementing the culture medium with various extracellular factors in order to improve the clinical outcome in IVF clinics. We may also contribute to the improvement of hESC derivation techniques and a better understanding of the distinct stem cell states.
The work on hESC is in collaboration with Prof. Mieke Geens (VUB), Prof. Karen Sermon (VUB), and Prof. Bjorn Heindryckx (UGent).
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