Deciphering the role of oligodendroglial Serpina3n in CPZ pathology using single-nucleus RNA sequencing

In this study, we employed single-nucleus RNA sequencing (snRNA-seq) to investigate cellular and transcriptional changes in the corpus callosum during demyelination induced by a 4-week CPZ diet. Samples were collected from three groups: (1) control mice maintained on a normal diet (Norm), (2) demyelinated mice fed a cuprizone diet (CPZ_Ctrl), and (3) cuprizone-treated mice with oligodendrocyte-specific deletion of Serpina3n (Olig2-Cre; Serpina3n flox/flox, CPZ_cKO).

This approach enabled dissection of cellular diversity and molecular pathways altered by CPZ-induced demyelination, with a particular focus on the role of oligodendroglial Serpina3n in regulating oligodendrocyte function. Our findings provide insight into cell-type-specific contributions to demyelination and identify Serpina3n as a potential therapeutic target. Overall, this study offers a comprehensive transcriptomic view of oligodendrocyte responses to demyelination, enhancing our understanding of their individual and collective roles in disease pathology.