Alterations in oligodendrocyte transcriptional networks reveal region-specific vulnerabilities to neurological disease

We identified region-specific co-expression networks representing distinct molecular pathways in oligodendrocytes associated with human neurological disease. Bioinformatic analyses reveal molecular regulators of these networks and, in this data, we confirmed modulation of network expression in vitro in a human cell line. This work supports identification of targetable region-specific vulnerabilities to neurological disease mediated by oligodendrocytes. Overall design: To validate the results of our systems-level analysis in mouse OLs and connect our observations to human biology and disease, we performed validation experiments using a human OL cell line (HOG) followed by RNA-seq and WGCNA to independently confirm the effects observed in the mouse models.