Defective Lamin A-Rb Signaling in Hutchinson-Gilford Progeria Syndrome and Reversal by Farnesyltransferase Inhibition
(A) Microarray plot profiles indicate changes in gene expression in control, HGPS, FTI-treated control and FTI-treated HGPS fibroblasts. Each continuous line corresponds to the normalized intensity value of an individual probe set. Line colors denote the intensity of the signal (red: strong and blue: low signal). Probes that satisfied a greater or less than two-fold cutoff and statistically significant difference of p <0.01 are displayed. (B) Pie chart indicates the predicted subcellular localization of proteins encoded by the 352 genes differentially expressed in HGPS. The list of differentially expressed genes in HGPS versus control cells was analyzed using Ingenuity Pathway Analysis (IPA) and encoded proteins assigned a subcellular localization based on information contained in the Ingenuity Knowledge Base. (C) Genes differently expressed in HGPS (352 genes) were assigned to diverse cellular functions using the “Functional Analysis” tool of IPA software (www.ingenuity.com). Columns represent groups of genes associated with specific cellular functions (x-axis). The significant genes were compared to IPA database and ranked according to a p-values generated with Fisher extract test. P-values less than 0.05 indicates a statistically significant, non-random association between a set of significant genes and a set of all genes related to a given function in IPA database. The ratio (y-axis) represents the number of genes from the dataset that map to the pathway divided by the number of all known genes ascribed to the pathway. The yellow line represents the threshold of p<0.05. (D) As described above, the 352 genes were assigned to diverse physiological systems according to IPA.