Project description:Klinefelter syndrome (KS) is the most prevalent aneuploidy in males and is characterized by an extra copy of the X chromosome,while the non-mosaic form of KS with 47,XXY karyotype is the most frequent (80-90%), less common non-disjunction events during the early mitotic division of the zygote result in mosaic forms of KS (47,XXY/46,XY). Here, using a paradigmatic cohort of KS-inducible pluripotent stem cells (iPSCs) carrying 47,XXY karyotypes we present the first iPSC-based disease-modeling study performed on KS patients from Saudi Arabia. We profiled the transcriptome of these Saudi KS-iPSCs, virtually characterized by subduedcgenetic backgrounds. Moreover, we performed a comparative transcriptomic analysis to assess the aberrant gene expression profile due to X dosage imbalance in four Saudi and five European and North American 47,XXY patients-derived iPSCs from our previously published study on KS and high-grade sex chromosome aneuploidies (SCAs). We identified a transcriptomic signature including ten PAR1 genes and thirteen non-PAR escape genes consistently upregulated in KS compared to 46,XY controls in both groups, as well as 193 consistenty disregulated autosomal genes. Our results indicate that the global transcriptional impact of X chromosome overdosage in KS is largely attributable to X-linked genes escaping X inactivation, regardless of the geographical area of origin, ethnicity, and genetic background.
Project description:Whole transcript expression was profiled using the Affymetrix 1.0 array in human bronchial epithelial cells exposed to PM collected from Saudi Arabia for 1 or 4 days. The differentially expressed genes were identified and analyzed for enriched networks and pathways using Ingenuity Pathway Analysis (IPA). We have identified 140 and 230 genes that significantly changed more than 1.5 fold after PM exposure for 1 or 4 days, respectively. IPA analysis revealed that different exposure durations triggered distinct pathways. Genes involved in NRF2-mediated response to oxidative stress were up-regulated after 1 day exposure. In contrast, cells exposed for 4 days exhibited significantly changes in genes related to cholesterol and lipid synthesis pathways.
