Identification of a Serum-Induced Transcriptional Signature Associated With Type 1 Diabetes in the BioBreeding Rat

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FIG. 1.
FIG. 1.

Analysis of genes commonly regulated by day 60 DR+/+ and DRlyp/lyp sera relative to allogeneic BN sera. PBMCs of four BN rats each were cultured under six different conditions: 1) autologous serum (n = 4 cultures), 2) autologous serum spiked with IL-1β (1 ng/ml, n = 4 cultures), 3) allogeneic BN serum (n = 15 cultures), 4) a DRlyp/lyp serum pool (n = 4 cultures), 5) a DRlyp/lyp serum pool supplemented with IL-1Ra (1 μg/ml, n = 4 cultures), and 6) DR+/+ serum pool (n = 4 cultures). The serum pools were created from an equal contribution of six individual male rats. Gene expression was measured independently in each culture, and all data were normalized with that of the autologous induction to account for gene expression induced by placing the PBMCs into culture. A: A Venn diagram illustrating the relationship between the gene expression induced in the DRlyp/lyp vs. BN allogeneic and DR+/+ vs. BN allogeneic inductions (|log2 ratio| > 0.5- ± 1.4-fold; ANOVA FDR <0.10). B: The mean expression of the five experimental conditions were examined for relatedness by hierarchical clustering using the commonly regulated probe sets (n = 912) of the DRlyp/lyp vs. BN allogeneic and DR+/+ vs. BN allogeneic intersection. Note the similarity between the DRlyp/lyp and DR+/+ signatures and the failure of IL-1Ra to highly influence the DRlyp/lyp signature for this subset of genes. C: Well-annotated genes regulated in BN PBMCs when cultured with either DRlyp/lyp or DR+/+ sera related to immune activation. *Orthologues regulated by human type 1 diabetes sera (13). The scale represents the fold of change between the serum tested relative to autologous serum (−fourfold to +fourfold).

This Article

  1. Diabetes vol. 59 no. 10 2375-2385