Genetics

This post covers Schirmer and colleagues' 2019 Nature study, which applied single-nucleus RNA sequencing and spatial transcriptomics to cortical grey matter and subcortical white matter from MS and control brains. It follows the archival cohort of patients who never received modern immunomodulatory therapy, the selective loss of CUX2-expressing upper-layer excitatory neurons while neighbouring interneurons and deeper excitatory neurons are spared, the pseudotime trajectory that orders the stress programme against degree of cortical demyelination, the in situ validation by single-molecule fluorescence hybridization, the lineage- and region-specific changes in astrocytes, oligodendrocytes and microglia, and the culture experiment testing whether myelin transcripts found in microglial nuclei are an artifact or real phagocytic transport.