MacLean M, López-Díez R, Vásquez C, Gugger PF, Schmidt AM (Submitted) Neuronal–glial communication perturbations in murine SOD1G93A spinal cord, Communications Biology, [doi:TBD](LINK TO PAPER).
Raw sequencing data, gene-barcode matrices, and metadata: NCBI GEO GSE173524
Amyotrophic lateral sclerosis (ALS) is an incurable progressive neurodegenerative disease characterized by proteinaceous aggregate accumulation and neuroinflammation. To interrogate cell-intrinsic and inter-cell-type perturbations in ALS, single-nucleus RNA sequencing was performed on the lumbar spinal cord in the murine ALS model SOD1G93A transgenic mice and littermate control mice at peri-symptomatic onset stage of disease, age 90 days. Our findings pinpoint perturbed tripartite synapse functions coupled with dysfunctional repair mechanisms and complement activation. These processes, together with metabolic stress, exacerbate cell-death and proteolytic stress-associated gene sets, even during incipient symptomatology at age 90 days. This work provides a new resource of cell-specific niches in the ALS spinal cord and asserts that intertwined neurodegenerative cellular processes are underway before disease manifestation and are recapitulated, in part, in the human post-mortem ALS spinal cord.
Shiny app designed by Paul Gugger based partly on code from nichExplorer