Donders Institute for Brain, Cognition and Behaviour
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Thesis defense Leenke van Haaften (Donders series 461)

16 December 2020

Promotors: prof. dr. ir. H. van Bokhoven, dr. N. Nadif Kasri
Co-promotor: dr. B. de Vries

Modeling Neurodevelopmental Disorders Using Human Pluripotent Stem Cells: From Epigenetics Towards New Cellular Mechanisms

Neurodevelopmental disorders (NDDs), are genetically and phenotypically highly heterogeneous and present a major challenge in clinical genetics and medicine. To improve the quality and efficiency of treatments, research to identify disease-causing mechanisms of these disorders is required. Therefore, recent advances in the field of iPSC technology were used to develop human in vitro models for Kleefstra syndrome and Koolen-de Vries syndrome to gain insights into neuronal abnormalities and underlying molecular mechanisms within a patient-specific genomic background. Both disorders are monogenic, caused by mutations in genes encoding for proteins that are part of the epigenetic machinery. Results help to increase our understanding of the complexity of epigenetic regulation in neural development and function. Furthermore, the findings provide new mechanistic insights and underlying mechanisms that might serve as promising starting points for the development of more targeted and efficient therapies.