Single-cell transcriptome sequencing to investigate mechanisms of epileptogenesis in genetic mouse models and human brain biopsy tissue
Molecular Biology and Physiology of Neurons and Glial Cells
Final Report Abstract
Despite the identification of a steadily increasing number of epilepsy genes and elucidation of molecular mechanisms of disease-causing mutations in simple expression systems, the exact mechanisms as to how epilepsy develops as a consequence of a genetic defect is poorly understood. Specifically, it remains elusive how genetic mutations and epileptogenesis are interconnected in the development of an epileptic phenotype in genetic epilepsy syndromes as well as at which time-points epileptic seizures start. Using state of the art sequencing techniques we, therefore, investigated in four separate projects of our DFG-funded research unit brain region- and time-specific RNA expression in distinct neuronal subpopulations of a conditional knock-in mouse model (Scn1a) and global knock-in mouse models (Scn2a, Kcna2) and in human samples from epilepsy surgical cases. Transcriptomic signatures of epileptogenesis were analyzed by single-nuclei RNA sequencing of hippocampal (CA1 and CA3), cortical and thalamic (nRT) neurons.
Publications
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Axonopathy and altered synaptic development in early hippocampal epileptogenesis of Dravet syndrome.
Layer, Nikolas; Müller, Peter; Ayash, Maya; Pfeiffer, Friederike; Saile, Meret; Klopfer, Fabian; Iavarone, Stefano; Santuy, Andrea; Fallier-Becker, Petra; Hedrich, Ulrike B. S.; Lerche, Holger; Koch, Henner & Wuttke, Thomas V.
