SLITRK2 knockdown in human motor neurons rescues axonal and functional neuromuscular deficits in FUS-ALS

The mechanisms underlying these changes are studied intensely but remain poorly understood. Here, we exploited FUS-ALS to interrogate cell compartment-specific changes in RNA expression and regulation.

To achieve this, we established a pipeline combining human induced pluripotent stem cell (iPSC)-derived MNs with microfluidic compartmentalization. We first validated this platform and characterized the human axonal transcriptome by performing 3'-tag RNA sequencing on paired soma and axon samples from three healthy control (HC) lines. Subsequently, we applied this pipeline to specifically investigate gene expression and alternative polyadenylation (APA) alterations in the axons of FUS-ALS MNs.