Genomic Regulators of Cell Fate

Our lab studies the origin and consequences of de novo variation in the genome of human pluripotent cells. These unique cells have the ability to become any cell type of the human body, both in vitro – in the form of human pluripotent stem cells- and in vivo – in the human preimplantation embryo. Interestingly, both are also very prone to genome instability.

In the 90s, studies using FISH on human preimplantation embryos revealed already that the early stages of human development are very prone to aneuploidies. These findings have been nothing but confirmed, and over the last decades, studies of the full chromosomal content of single cells have now fully characterized the extend of the genome instability in human embryos. In the past, our lab has worked on characterizing the levels of abnormality in embryos, and in more recent work, we have studied the mechanisms behind the origin of aneuploidy and the selective clearance of abnormal cells in the blastocyst stage. Further research is now directed towards understanding the impact of aneuploidy on the second lineage segregation event and on gastrulation, using human pluripotent stem cells as a model.

Human pluripotent stem cells are the in vitro counterpart of the embryonic epiblast, and come in two flavors: human embryonic stem cells (hESC) are derived from blastocyst-stage embryos, and human induced pluripotent stem cells (hiPSC), which are obtained by the reprogramming of somatic cells.

Human pluripotent stem cells not only hold a great promise in the field of regenerative medicine because of their potential to develop into any cell type of the adult individual, but are, because of this same potential, an incredibly powerful tool to research early developmental processes.

Intensive research over the past decades has yielded numerous protocols for the differentiation of human pluripotent stem cells into virtually any cell type, and the first steps towards the clinic have been taken. Currently, one of the key issues in this regard is the genomic stability of these cells during culture. We and others have shown that they are prone to chromosomal abnormalities, including aneuploidies, fragile site expression and small duplications with a hotspot at 20q21.11. This genomic instability strongly reminds of the behavior of cancer cells, and is of great concern for the use of pluripotent stem cells for therapeutic purposes or as reliable research models.

In our lab, we have a long track-record in the study of the origin, extent and consequences of this genetic instability, our current focus being understanding their role in modulating cell specification and in priming differentiated cells for oncogenic transformation.

Finally, our lab has been studying mitochondrial genome variance in preimplantation development, pluripotent stem cells and more recently in individuals born after fertility treatments.

Fonds voor Wetenschappelijk onderzoek Vlaanderen

Agentschap voor innovatie door wetenschap en techniek

Methusalem grant of the Research Council of the Vrije Universiteit Brussel

Scientific Research Fond Willy Gepts of Universitair Ziekenhuis Brussel, Vrije Universiteit Brussel