Gene expression profile in spleens of congenic mice 24 hours after total body irradiation.
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
SUBMITTER: Thai Cao
PROVIDER: E-GEOD-44431 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
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Project description:A major challenge in bone allogeneic marrow (BM) transplantation is overcoming engraftment resistance to avoid the clinical problem of graft rejection. Identifying genes and pathways that regulate BM engraftment may reveal molecular targets for overcoming these engraftment barriers. Previously, we developed a mouse model of BM transplantation that utilizes recipient conditioning with non-myeloablative total body irradiation followed by transplantation of allogeneic BM cells. We defined TBI doses that lead to graft rejection, that are permissive for engraftment, and mouse strain variation with regards to the permissive TBI dose. We now report gene expression analysis, using the Agilent Mouse 8x60K v3 expression arrays, in spleen of mice conditioned with TBI doses for evaluation in correlation to the expected engraftment phenotype. The spleens of mice given TBI demonstrated extensive differential gene expression, compared with un-irradiated controls, at both multiple testing-corrected P < .05 and fold change greater than or equal to 2 levels. Functional analysis revealed significant enrichment for up-regulation of canonical pathways involved in inflammation, even when treated with TBI doses not permissive for engraftment. Consistent with this the most significantly associated upstream regulators included lipopolysaccharide, tumor necrosis factor, and a toll-like receptor. Unique to engrafting mice, however, were enrichment for a down-regulated canonical pathway related to B-cell development. Results from this analysis have identified canonical pathways and upstream regulators of BM engraftment in mice and may lead to new approaches to overcome the problem of graft rejection complicating clinical BM transplantation. Each individual sample was pooled from 3 mice and performed in triplicate for each experimental group (TBI 300 cGy, 400 cGy, or 500 cGy) and for each strain mice (BALB.K or B10.BR) for statistical analysis. Additional arrays were perfromed for TBI 800 cGy (BALB.K) and TBI 900 cGy (B10.BR) for anlaysis of gene expressive after myeloablative condition.
2013-01-08 | E-GEOD-43310 | biostudies-arrayexpress
Project description:The Gvh1 gene loci was identified by linkage analysis in a segregating mouse backcross. Congenic mapping has refined the linked loci to a 1.3 Mb interval on mouse Chr16 (39.41 - 40.71Mb) that constitutes the congenic interval in the B10.BALB-16.C2A mouse line. Gene expression microarray was performed to characterize downstream transcripitional regulation by risk variants in the congenic interval;.
2013-02-21 | GSE44431 | GEO
Project description:Previous work has demonstrated the potential for peripheral blood (PB) gene expression profiling for the detection of disease or environmental exposures. We have sought to determine the impact of several variables on the PB gene expression profile of an environmental exposure, ionizing radiation, and to determine the specificity of the PB signature of radiation versus other genotoxic stresses. Keywords: peripheral blood, gene expression study, radiation reponse We have sought to determine the impact of several variables on the PB gene expression profile of an environmental exposure, ionizing radiation, and to determine the specificity of the PB signature of radiation versus other genotoxic stresses. Neither genotype differences nor the time of PB sampling caused any lessening of the accuracy of PB signatures to predict radiation exposure, but sex difference did influence the accuracy of the prediction of radiation exposure at the lowest level (50 cGy). A PB signature of sepsis was also generated and both the PB signature of radiation and the PB signature of sepsis were found to be 100% specific at distinguishing irradiated from septic animals. We also identified human PB signatures of radiation exposure and chemotherapy treatment which distinguished irradiated patients and chemotherapy-treated individuals within a heterogeneous population with accuracies of 90% and 81%, respectively. Human and Murine samples used in models Peripheral blood was collected from patients prior to and 6 hrs following total body irradiation with 150 to 200 cGy as part of their pre-transplantation conditioning. For additional comparison, peripheral blood was obtained from healthy volunteers and an additional cohort of patients prior to and 6 hrs following the initiation of alkylator-based chemotherapy alone (without radiotherapy).
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Project description:External ionizing Irradiation of pregnant mice at E13.5 4 Gy, gene expression at E17.5 On E13.5, female C57Bl/6HN mice were irradiated (total body) at 0 Gy (sham) or 4 Gy using a Gamma Cell cesium irradiator (JL Shepherd, San Fernando, CA), with a dose rate of 70 cGy/min. The mice were monitored for 4 days, and on E17.5, they were sacrificed, and placentas were procured and processed for RNA extrtaction.
2013-08-16 | E-GEOD-49923 | biostudies-arrayexpress
Project description:We examined molecular responses using transcriptome profiling in isolated left ventricular murine cardiomyocytes to 90 cGy, 1 GeV proton (1H) and 15 cGy, 1 GeV/nucleon (n) proton (56Fe) particles 1, 3, 7, 14 and 28 days after exposure. Unsupervised clustering analysis of gene expression segregated samples according to the radiation (IR) response, and time after exposure with 56Fe-IR showing the greatest level of gene modulation. 1H-IR exposures showed little differential transcript modulation. Network analysis categorized the major differentially expressed genes into cell cycle, oxidative responses and transcriptional regulation functional groups. Transcriptional networks identified key nodes regulating expression. Individual transcription factors were inferred to be active at 1, 3, 7, 14 and 28 days after exposure. Validation of the signal transduction network by protein analysis showed that particle IR clearly regulates a long lived signaling mechanism for p38 MAPK signaling and NFATc4 activation. Electrophoresis mobility shift assays supported the role of additional key transcription factors GATA-4, STAT-3 and NF-κB as regulators of the response at specific time points. These data suggest that the molecular response to 56Fe-IR is unique and shows long-lasting gene expression in cardiomyocytes, up to 28 days after exposure. Additionally, proteins involved in signal transduction and transcriptional activation via DNA binding play a role in the response to high charge (Z) and energy (E) particles (HZE). Our study may have implications for NASAâs efforts to develop heart disease risk estimates for astronauts safety via identification of specific HZE-IR molecular markers and for patients receiving conventional and particle radiotherapy. Transcriptome profiling in isolated left ventricular murine cardiomyocytes to 90 cGy, 1 GeV proton (1H) and 15 cGy, 1 GeV/nucleon (n) proton (56Fe) particles 1, 3, 7, 14 and 28 days after exposure.
2016-07-03 | E-GEOD-68875 | biostudies-arrayexpress
Project description:We examined molecular responses using transcriptome profiling in isolated left ventricular murine cardiomyocytes to 90 cGy, 1 GeV proton (1H) and 15 cGy, 1 GeV/nucleon (n) iron (56Fe) particles 1, 3, 7, 14 and 28 days after exposure. Unsupervised clustering analysis of gene expression segregated samples according to the radiation (IR) response, and time after exposure with 56Fe-IR showing the greatest level of gene modulation. 1H-IR exposures showed little differential transcript modulation. Network analysis categorized the major differentially expressed genes into cell cycle, oxidative responses and transcriptional regulation functional groups. Transcriptional networks identified key nodes regulating expression. Individual transcription factors were inferred to be active at 1, 3, 7, 14 and 28 days after exposure. Validation of the signal transduction network by protein analysis showed that particle IR clearly regulates a long lived signaling mechanism for p38 MAPK signaling and NFATc4 activation. Electrophoresis mobility shift assays supported the role of additional key transcription factors GATA-4, STAT-3 and NF-κB as regulators of the response at specific time points. These data suggest that the molecular response to 56Fe-IR is unique and shows long-lasting gene expression in cardiomyocytes, up to 28 days after exposure. Additionally, proteins involved in signal transduction and transcriptional activation via DNA binding play a role in the response to high charge (Z) and energy (E) particles (HZE). Our study may have implications for NASAâ??s efforts to develop heart disease risk estimates for astronauts safety via identification of specific HZE-IR molecular markers and for patients receiving conventional and particle radiotherapy. Transcriptome profiling in isolated left ventricular murine cardiomyocytes to 90 cGy, 1 GeV proton (1H) and 15 cGy, 1 GeV/nucleon (n) iron (56Fe) particles 1, 3, 7, 14 and 28 days after exposure.
2016-07-03 | E-GEOD-68874 | biostudies-arrayexpress
Project description:The goal of this experiment was to identify genes contributing to fat, carbohydrate, and total calorie intake in mice by comparing gene expression in liver and hypothalamus of an interval-specific congenic strain, B6.CAST-17, with that of the control strain. This congenic strain has previously confirmed genetic loci on Chr 17 linked to increased carbohydrate (Mnic1) and kilocalorie (Kcal2) intake. Keywords: Comparative gene expression analysis
2007-12-11 | GSE6507 | GEO
Project description:We previously utilized interval-specific congenic lines derived from C57BL/6J (B6) and DBA/2J (D2) alleles to fine map a quantitative trait locus (QTL) influencing methamphetamine (MA)- induced locomotor activity. We identified a 0.23 MB critical interval on chromosome 11 containing only two protein coding genes, Rufy1 and Hnrnph1. Notably, Rufy1 contains three missense SNPs and Hnrnph1 contains 1 SNP near the 5’ UTR. In an effort to identify the molecular mechanisms that bridge genetic variation with behavior, we conducted transcriptome analysis via mRNA sequencing (RNA-seq) in a B6.D2 congenic line (chr.11: 50-60 Mb) that captures the QTL. There was an overrepresentation of cis-regulated, differentially expressed genes within the congenic interval (4 out of 92 differentially expressed genes; FDR < 0.05) and widespread genomic regulation on all autosomes.
2015-12-11 | GSE66366 | GEO
Project description:The 112kb congenic was identified via routine monitoring of the proximal and distal SNP sites of the heterozygous Line 4a C57Bl/6J (B6J)-DBA/2J (D2J) congenic offspring (PMID: 26658939). The 112kb congenic was identified via routine monitoring of the proximal and distal SNP sites of the heterozygous Line 4a C57Bl/6J (B6)-DBA/2J (D2) congenic offspring (Yazdani et al. 2015). Like the Line4a congenic, the original mouse of interest possessed a D2J SNP site at the proximal end of the D2J interval (rs29383600; mm9 - chr11:50,186,508, mm10 - chr11:50,373,006). To identify the distal D2J boundary of this new congenic, we generated a list of known SNPs within a roughly 55kb interval spanning downstream from the distal end of the originally characterized 206kb “critical interval” harboring Hnrnph1 and Rufy1 (mm9 - chr11:50,295,887-50,352,284, mm10 - chr11:50,482,385-50,538,782). Starting from the upstream portion of the interval, PCR primers were designed to every five SNPs, and 200bp region around each SNP was amplified, run on a 1.5% agarose gel, visualized for band specificity. Single appropriately-sized bands were then excised and gel purified (Promega Wizard SV Gel and PCR Clean-Up System, Cat A9281), and prepared for sanger sequencing (Genewiz). Using the SNP data from the Mouse Genome Project (Sanger Institute) for reference, the sequenced SNPs were deemed as either heterozygous for B6J and D2J SNPs or homozygous/wildtype B6J. The final SNP we identified as D2 was rs29459915 (mm9 - chr11:50,297,762, mm10 - chr11:50,484,260), and the first SNP we identified as B6 was rs254771403 (mm9 - chr11:50,300,250, mm10 - chr11: 50,486,748).
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2009-06-08 | E-GEOD-14466 | biostudies-arrayexpress