Single-Cell Genomics Reveals Spatial and Stage-Associated Diversity in Multiple Sclerosis (P2.2-070)

Objective: To dissect cellular heterogeneity and understand molecular changes in inflammatory cells, neurons and glial cell types by single-cell genomics of MS and control brain samples.Background: Multiple sclerosis (MS) is a chronic inflammatorydemyelinating disease with early relapsing-remitting and late progressive phases. Neurodegeneration and astrogliosis accompany lesion formation with damage and loss of oligodendrocytes.Design/Methods: We utilized single-nucleus RNA sequencing (snRNAseq) and multiplex in situ hybridization to dissect transcriptional profiles of inflammatory cells, neurons and glial cell types during MS lesion progression.Results: Phase-associated signatures were primarily driven by upregulation of long-noncoding RNAs and cell stress pathway genes in projection neurons and oligodendrocytes. We identified selective loss of excitatory cortical projection neurons in areas …