Spatial characterization of the motor and non-motor somal and axonal transcriptome in adult healthy and mutant FUS mice

Here we investigated the transcriptome of motor and non-motor axons and cell bodies in the context of mutant FUS-related amyotrophic lateral sclerosis (ALS). We applied Nanostring GeoMX Digital Spatial Profiler platform to profile the transcriptome of subcellular compartments in the lower motor circuitry of a mouse model ricapitulating ALS motor symptoms. This work sheds light for the first time on the transcriptomic alterations in axons and in somas which may contribute to axonal degeneration and neuromuscular junction denervation, early features of ALS. Overall design: Four 5-um thick spinal cord and sciatic nerve sections derived from control and humanized FUS R521H mice were layered on normal glass microscope slides and sent to Nanostring Technologies facility in dry ice (Seattle, US). Slides were analyzed on the Nanostring GeoMx Digital Spatial Profiler platform using the Whole Mouse Transcriptome Atlas panel (Nanostring). Regions of interest were drawn on spinal cord ventral horns and full sciatic nerve sections, and further segmented into ChAT+ and ChAT- areas of interest.