Molecular characteristics of microglia in APOE-/-mice treated with APOE130-149 or control peptides after NMOSD induction
NMOSD is an autoimmune astrocytopathy of the central nervous system, mediated by antibodies against aquaporin-4 water channel protein (AQP4-Abs), resulting in damage of astrocytes with subsequent demyelination and axonal damage. The extracellular communication through astrocyte-derived extracellular vesicles (ADEVs) has received a growing interest in association with astrocytopathies, however, to which extent ADEVs contribute to NMOSD pathogenesis remains unclear. Here, we demonstrate a significant increase in apolipoprotein E (APOE)-rich ADEVs in AQP4-Abs-positive NMOSD patients as well as in a murine model of NMOSD.To capture further insight regarding the effects of APOE on microglial functional status, scRNA-seq was performed to identify molecular characteristics of microglia of APOE-/- mice subjected to sham or NMOSD induction and treated with APOE130-149 or control peptides. We demonstrated  that APOE130-149 treatment has a substantial effect on microglial transcriptomes and biological features, suppressing molecules associated with microglia activation and pro-inflammatory functions. Overall design: To capture insight regarding the effects of APOE on microglial functional status, scRNA-seq was performed to identify molecular characteristics of microglial cells of APOE-/- mice subjected to sham or NMOSD induction and treated with APOE130-149 or control peptides. CD45intCD11b+ cells were sorted from the mouse brain by flow cytometry on day 4 after NMOSD induction, and were subjected to single cell RNA sequencing. Data were pooled from 4 mice each group.