Figure 1
From: Human WRN is an intrinsic inhibitor of progerin, abnormal splicing product of lamin A
Gene ontology analysis of HGPS and WRN cells. (A) Heatmap of gene expression profiles in normal fibroblasts (young; N9; unaffected 9-year old subject, and aged; N81; unaffected 81-year-old subject) and prematurely aged cells (HGPS and WRN) at passage 10. Microarray was performed using Human Gene 1.0 ST arrays (Affymetrix). Yellow boxes indicate gene sets downregulated in both WRN and HGPS cells compared to normal fibroblasts (N9). Blue boxes indicate gene sets upregulated in both WRN and HGPS cells compared to N9 fibroblasts. White boxes indicate gene sets common to N81 fibroblasts as well as WRN and HGPS cells compared to N9 fibroblasts. (B) Analysis of differentially expressed genes (DEGs) showing a more than twofold difference from N9 fibroblasts. A total of 285 genes (core gene set) were commonly altered in progeroid cells (WRN and HGPS) and N81 fibroblasts compared to N9 fibroblasts. (C) Downregulated genes in the core gene set are associated with the cell cycle, chromosome separation, DNA replication, and DNA repair in HGPS, WRN, and N81 fibroblasts. Gene clustering was performed using the gene interaction mapping tool in cBioPortal (http://www.cbioportal.org). (D) DEG analysis (at least twofold) of HGPS and WRN cells compared to N9 fibroblasts. A total of 881 genes were altered in both HGPS and WRN cells. (E) Nine common elements overlapped between HGPS and WRN, including cell cycle regulation and chromosome separation. (F) Compared to normal fibroblasts (at passage 10), the expression of BRCA1, cyclin B1, cdc25c, rad51, H3K9me3, and p16INK4A in HGPS and WRN cells (at passage 10) was reduced. Western blots were cropped from different parts of the same samples and analyzed by film-based imaging systems (n = 3 independent experiments; two-tailed Student’s t-test).
