Project description:Intermittent hypoxia (IH) is a hallmark of obstructive sleep apnea (OSA), which has been proposed as the major determinant of processes involving tumor invasion and metastasis. To study whether circulating DNA (cirDNA) in blood plasma reflects the changes that the tumor cells undergo under IH conditions, we used a xenografted murine model. Mice engrafted with TC1 epithelial lung and controls were exposed to IH or room air (RA) conditions. Plasma cirDNA amounts were significantly increased in mice exposed to IH (p<0.05). We found a significant correlation between plasma cirDNA concentration and tumor size, weight and invasiveness (p<0.05). Using a microarray-based approach, we identified 2,094 regions showing significant differential cirDNA modifications. System biology analysis revealed an association with molecular pathways misregulated in cancer progression and with distal and TSS-associated transcription factor binding sites. We detected clusters of highly variable regions in chromosomes 7, 13, 14 and X, which may highlight hotspots for DNA deletions. Single locus displayed high intragroup variation, suggesting cellular heterogeneity within the tissue may be associated to cirDNA release. Our result showed that exposure to IH increases the shedding of cirDNA into circulation, which carries epigenetic modifications that may characterize cell populations within the tumor that preferentially release their DNA upon IH exposure. 6 xenografted mouse samples were analyzed by microarray analysis: Mouse exposed to IH (n=3, XenoIH group) and mouse exposed to room air conditions (n=3, XenoRA group)
Project description:Intermittent hypoxia (IH) is a hallmark of obstructive sleep apnea (OSA), which has been proposed as the major determinant of processes involving tumor invasion and metastasis. To study whether circulating DNA (cirDNA) in blood plasma reflects the changes that the tumor cells undergo under IH conditions, we used a xenografted murine model. Mice engrafted with TC1 epithelial lung and controls were exposed to IH or room air (RA) conditions. Plasma cirDNA amounts were significantly increased in mice exposed to IH (p<0.05). We found a significant correlation between plasma cirDNA concentration and tumor size, weight and invasiveness (p<0.05). Using a microarray-based approach, we identified 2,094 regions showing significant differential cirDNA modifications. System biology analysis revealed an association with molecular pathways misregulated in cancer progression and with distal and TSS-associated transcription factor binding sites. We detected clusters of highly variable regions in chromosomes 7, 13, 14 and X, which may highlight hotspots for DNA deletions. Single locus displayed high intragroup variation, suggesting cellular heterogeneity within the tissue may be associated to cirDNA release. Our result showed that exposure to IH increases the shedding of cirDNA into circulation, which carries epigenetic modifications that may characterize cell populations within the tumor that preferentially release their DNA upon IH exposure.
Project description:Expression data from mice exposed to intermittent hypoxia and mice reared for 12 months. We used microarrays to analyze the transcriptome of hippocampus from mice exposed to intermittent hypoxia or aged mice.
Project description:We hypothesize that the culture media collected from macrophages exposed to intermittent hypoxia will induce a greater pro-inflammatory gene profile in naïve cultured macrophages than will culture media collected from macrophages exposed to sustained hypoxia. We will evaluate gene expression using microarray analysis of RNA collected from RAW 264.7 macrophages cultured for 24 hours in DMEM media obtained from 1) cells cultured with intermittent hypoxia (2 minute cycles: 90 seconds at 40 Torr and 30 seconds at 8 Torr), 2) media exposed to intermittent hypoxia, 3) cells cultured with sustained hypoxia (8 Torr), 4) media exposed to sustained hypoxia and 4) standard tissue culture conditions (fresh DMEM media; reference).
Project description:We exposed p14 mice to 56 day of forced intermittent hypoxia as a proxy stimlulus for pediatric OSA. After this exposure, we performed sn-RNA seq of the hippocampus of both normoxic controls and IH exposed mice to study potentially DEGs.
Project description:We collected whole genome testis expression data from hybrid zone mice. We integrated GWAS mapping of testis expression traits and low testis weight to gain insight into the genetic basis of hybrid male sterility.