Early mammalian development and its regulation

Early mammalian development and its regulation

Dr Vincent Pasque

KU Leuven

The Pasque laboratory aims to understand the developmental programs that shape the early human embryo. Specifically, we are interested in how the first cellular lineages are generated and how gene regulatory programs are controlled.

Our lab identified chromatin regulators that oppose the induction of alternative cell fates during somatic cell reprogramming. We have characterized new stem-cell based early human post-implantation models and showed that human naive pluripotent stem cells model human extraembryonic mesoderm development. We have also contributed to understanding the epigenetic reprogramming process of X-chromosome reactivation. Recently, we discovered that mammalian cells possess intrinsic chromatin regulatory mechanisms that counteract X-chromosome gene dosage imbalances caused by evolutionary and in vitro X-chromosome loss as well as X-chromosome inactivation in mammalian cells.

Towards our aims, we use a variety of mammalian systems including 2D and 3D human and mouse pluripotent stem cell-based embryo and reprogramming models including human blastoids and induced pluripotent stem cell reprogramming. We are particularly interested in X-chromosome inactivation as a paradigm to study epigenetic mechanisms during development. The methods we use are interdisciplinary and include single-cell (multi)omics, advanced imaging and computational approaches. For perturbations we use CRISPR, RNA interference and drug treatments. The outcome of perturbations are then analysed and validated using a variety of assays including the use of human embryos.

In the first part of the talk, I will present our discovery that mammalian cells can sense the number of active X chromosomes present in a cell and adapt gene dosage accordingly. I will present our efforts to chart the chromatin dynamics and gene expression changes that take place during somatic cell reprogramming to iPS cell.

In the second part, I will present a new 2D model of early human postimplantation embryogenesis. I will show that primate-specific cell diversification after implantation including the extraembryonic mesoderm primary blood progenitor lineage can be modelled using human naïve pluripotent stem cells.

In the third part, I will present our efforts to use single-cell multi-omics to reconstruct the gene regulatory programs of early human embryos and comprehensively analyse the effects of chromosomal defects on developmental progression, gene expression and the gene regulatory networks underlying human pre-implantation development.

2006 BSc, MSc in Biochemistry, University of Liege, Belgium

2007 MPhil University of Cambridge, UK

2012 PhD University of Cambridge, UK

2012-2015 Postdoc UCLA, USA

2015 Group leader & Assistant professor, KU Leuven, Belgium

2020 Group leader & Associate professor, KU Leuven, Belgium

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