RNAseq of motor neurons with differential vulnerability to ALS isolated from the SOD1G93A mouse model of ALS

ALS is characterised by thedegeneration of somaticmotor neurons (MNs), that control voluntary muscle, while visceral motor neurons remain preserved. Some somatic motor neurons are also relatively resilient to degeneration, including oculomotor and trochlear motor neurons that regulate eye movement.In this study we aim to investigate the longitudinal transcriptional dynamics of resistant and vulnerable MN populations in response to the SOD1G93A ALS-causative mutation. We have conducted bulk RNA sequencing of MNs isolated from the SOD1G93A mouse at presymptomatic (p56) and symptomatic (p112) stages using laser capture microdissection followed by Smart-seq2 RNA sequencing. Oculomotor and trochlear (CN3/4) MN, and visceral MNs from the vagus nucleus (CN10) represent resilient neuron groups that were analysed. MNs from the lumbar spinal cord (SC) and hypoglossal (CN12) nucleus were utilised as two vulnerable populations. We used laser capture microdissection to isolate discrete neurons from transgenic SOD1G93A mice and wildtype littermates (Jax Stock No 00435). We analyzed a total of 54 samples with 3-5 biological replicates per condition. We included four neuronal groups with differential vulnerability in ALS and investigated two time points troughout disease progression including pre-symptomatic stage and symptomatic stage (P56,P112)