A multi-omics characterization of the human lumbar spinal cord and motor cortex reveals non-overlapping molecular signatures in ALS [snRNA-Seq; snATAC-Seq]

While motor neurons (MNs) are the selectively vulnerable cell type, their interactions with glia contribute to the progression of ALS pathology. However, it remains unclear whether the molecular alterations underlying MN and glial dysfunction in ALS are the same in the MTC and lumbar SC (LSC).

To address this, we constructed spatially-resolved gene expression maps of the MTC and LSC by combining spatial and single-nucleus transcriptomic profiles from a cohort of non-neurological controls and ALS patients clinically stratified by site of symptom onset. In the ventral horn of the LSC, we see a decrease in genes associated with MNs and synaptic signaling in ALS patients. We also identify region-specific alterations in endothelial- and glial-related functions.