Figure 3.
(A,B) K-means clustering for brain and spleen microarray data from two models. (A) A radar chart of 14 cluster center genes whose log ratios were higher than 1 or lower than −1, at least in one organ or in one mouse strain, compared with controls, among the total 35 clusters. (B) Dynamic expression patterns of four clusters. AB, SB, AS, and SS indicate A.SW mouse brain, SJL/J mouse brain, A.SW mouse spleen, and SJL/J mouse spleen, respectively. We used microarray data from three PP-EAE and three naïve mice of each strain (the total number of mice = 12). Genes in cluster 3 were up-regulated in the spleens of both models. Genes in cluster 8 were up-regulated in the brains of SJL/J mice. Genes in cluster 22 were down-regulated in the spleens of both models. Genes in cluster 25 were up-regulated in the brains of both models. (C–H) Gene networks up-regulated in the brains or down-regulated in the spleens from two models. Transcriptome data at disease peak were clustered and categorized by the Ingenuity Pathway Analysis (IPA) Network Generation. (C) The top network in the brains of A.SW mice was categorized as “Cell-To-Cell Signaling and Interaction,” “Hematological System Development and Function,” and “Immune Cell Trafficking,” which were composed of Fc receptor and complement-related genes. (D) The top network in SJL/J mouse brain was categorized as “Immunological Disease,” “Endocrine System Disorders,” and “Gastrointestinal Disease,” which were composed of IFN-α/β-induced genes and nitric oxide synthase 2 (Nos2). (E) The top network in A.SW mouse spleen was categorized as “Cell Cycle,” “Reproductive System Development and Function,” and “Cancer” which were composed of cell cycle-related genes. (F) The top network in SJL/J mouse spleen was categorized as “Small Molecule Biochemistry,” “Hematological Disease,” and “Metabolic Disease” which were composed of GATA1- and transporter-related genes. (G,H) Up- or down-regulated genes associated with MOG in the brains of A.SW mice (G) and SJL/J mice (H). Pro-inflammatory genes were down-regulated in A.SW mice and up-regulated in SJL/J mice, while Th2-associated genes were up-regulated in A.SW mice and down-regulated in SJL/J mice. Red and blue nodes indicate up- and down-regulated genes, respectively. Solid and dashed lines indicated direct and indirect connections, respectively. Score = network score.