Journal: bioRxiv

Article Title: Chronic Mild Stress Impairs Hippocampal Myelination through SOX6-Dependent Dysfunction of Oligodendrocyte Lineage Cells

doi: 10.64898/2026.05.29.728722

Figure Lengend Snippet: (A) Dot plot summarizing eRegulons with significantly altered activity between control and stress groups within each cell cluster. (B) Fourteen of the 36 TFs driving the stress-responsive eRegulons shown in (A) are associated with mental disorders, based on cross-referencing with the DisGeNET database. (C) While Sox6 transcript expression was not significantly altered in OPCs under stress ( left ), the activity of Sox6 -mediated eRegulons was significantly reduced ( right ). (D) OPCs were re-clustered based on eRegulon activity. Feature maps illustrate decreased activity of Sox6 -mediated eRegulons under stress at the single-nucleus level. (E) Network analysis revealed that Sox5 - and Sox6 -mediated eRegulons cooperate to regulate a complex gene network through their enhancers. The inner circle displays potential enhancers (snATAC peaks, represented by “♦”) linking SOX5 / SOX6 to their downstream targets, which are shown in the outer circle (represented by “●”). “Group Log2FC” quantifies the differential expression of target genes, and ‘rho_R2G’ represents the correlation coefficient between each candidate enhancer and its associated target genes. Genes that are OPC marker genes and/or significantly altered by stress are labeled. Eight genes involved in glutamatergic signaling and significantly downregulated in stressed OPCs are highlighted in gray boxes. (F) SOXD regulatory target genes identified by SCENIC+ were subjected to Metascape gene annotation and enrichment analysis. The left panel shows the top 20 significantly enriched terms, with terms related to cell migration, cell morphogenesis, and cell-cell/cell-matrix interactions highlighted by red, green, and blue arrows, respectively. The right panel shows the enrichment network of these terms. Each node represents an enriched term, with node size proportional to the number of associated genes. Terms with a similarity score > 0.3 are connected by edges, and edge thickness reflects the similarity score. (G) Hippocampal sections from control and stressed mice were subjected to immunofluorescence staining for OLIG2 (green) and SOX6 (red), with nuclei counterstained by DAPI (blue). Arrows indicate representative OLIG2⁺/SOX6⁺ double-positive cells. Scale bar, 20 µm. ( H ) Quantification of SOX6 immunoreactivity in OLIG2⁺/SOX6⁺ cells. N=7-8 sections from 4 mice per group, with at least 50 cells measured per mouse. **: p <0.01, by unpaired two-tailed Student’s t test. Data are mean ± SEM.

Article Snippet: Primary antibodies were applied overnight at 4 °C, including Olig2 (Synaptic Systems, #292015) (1:100), PDGFRα (Abcam, #ab203491) (1:400), and MBP (Abcam, #ab218011; 1:400).

Techniques: Activity Assay, Control, Expressing, Quantitative Proteomics, Marker, Labeling, Migration, Immunofluorescence, Staining, Two Tailed Test