Single-cell profiling of remyelination in the LPC model

Remyelination is reparative process by which axons that have lost their supportive insulation are re-encased in myelin. Multiple cell types are known to participate in this process, but their transcriptional dynamics from initial injury to full repair remain poorly characterized. Here, we combined high-throughput single-nucleus RNA-seq with Slide-seq, a high-resolution spatial transcriptomics technology, to densely reconstruct the cellular processes that coordinate remyelination after lysolecithin injection. First, we found extensive transcriptional diversity of glia and monocyte-derived macrophages from damage to repair. Second, we identified a population of infiltrating peripheral immune cells-- mostly CD8 T-cells and natural killer cells--that are enriched specifically during remyelination. Thirdly, we identified a concerted Interferon-response signature that is shared across several glial cell types--microglia, astrocytes, and oligodendrocyte lineage--just prior to reestablishment of myelin