Engineering neurons with hallmarks of cortical interneurons viain vivo lineage reprogramming

Prof. Benedikt Berninger - King's College London (KCL)
Engineering neurons with hallmarks of cortical interneurons viain vivo lineage reprogramming

Abstract
Glia-to-neuron lineage reprogramming emerges as an experimental strategy for cell-based brain repair. Using early postnatal cerebral cortex as an experimental model, we explore the possibility of lineage converting cells of the astro- and oligodendroglial lineages into neurons with molecular and electrophysiological hallmarks of cortical interneurons. By exploiting a mutant variant of the proneural transcription factorAscl1 which exhibits heightened neurogenic activity, we found that astroglial cells can be reprogrammed into neuronsexhibiting hallmarks of parvalbumin-expressing fast spikinginterneurons. In this lecture, I will discuss our efforts to leverage single cell transcriptomics to unravel the molecular underpinnings of the conversion process. Also, I will present data that indicate the incorporation of glia-derived neurons intocortical circuits processing sensory input.