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Autism spectrum disorders: From dynamic developmental disease trajectories to gene network heterochronicity

DZNE talk

Datum:27.06.2019, 13:00 - 14:00
Sprecher: Dr. Simon Schafer, Laboratory of Genetics, SALK Institute for Biological Studies
Ort: CRTD, auditorium right
Gastgeber: Dr. Tomohisa Toda (DZNE)

Abstract
Autism is a neurodevelopmental disorder with a complex genetic etiology. Recent advances in systems biology approaches have caused a paradigm shift in the field from a single gene causation model to pathway perturbation models and the cellular and molecular events that lead to autism likely occur very early during human fetal cortical development. However, one of the current challenges in understanding autism pathophysiology is to determine critical neurodevelopmental periods and cellular states that might provide the ground for disease propensity. This task requires an in-depth exploration of the temporal dimension of shifting biological processes by treating the disorder as an evolving, dynamic system. Using a time series approach to monitor patient-derived induced pluripotent stem cells (iPSCs) throughout early stages of neurodevelopment enabled us to reconstruct the dynamics of transcriptional gene network programs and led to the identification of an intrinsic network-specific heterochronicity. Our data show that these ASD-related changes are likely to be primed during an earlier stage of development and we propose that studying molecular disease trajectories could maximize our chance of capturing relevant mechanistic disease states, as well as the processes by which these states unfold.

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