Figure 4.

MBH oligodendrocyte response to pancreatic cancer. Top-induced genes in oligodendrocytes in TB mice ranked by fold inductions (A). Featureplots showing the induction of genes in oligodendrocytes linked to fatty acid synthesis, stress and cell adhesion (B). DE genes between sham and TB mice in oligodendrocytes as shown with a volcano plot (C). ISH against Plin4 reveals increased Plin4 expression in brain sections of TB mice compared to sham (D). qPCR analysis for Plin4 and Pnpla2 using whole hypothalamic RNA extracts from sham and TB mice (E). Proposed model whereby the stress-responsive genes Sgk1 and Cirbp are proposed to act as master regulators of the cachexia response in oligodendrocytes by regulating genes linked to catabolism of fatty acids and starvation conditions (F). Co-expression network using the top-induced genes in oligodendrocytes revealing a network linked to transmission across chemical synapses. The subnetwork of co-regulated genes is highlighted, and violin plots on the right showing the expression of network members for sham and TB mice (G). ISH against Ptgds reveals increased expression in brain sections of TB mice compared to sham, also shown is the quantification (H). The increase in Ptgds and integrins is proposed to impact communication between cell types in the MBH. Scale bar = 100 μm. Graph values represent the mean ± SEM of at least three independent experiments and statistical significance between groups was determined with a Student's t-test (∗P < 0.05, ∗∗P < 0.01, ∗∗∗P < 0.001).