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SRP061686
Bos taurus
40 Downloadable Samples
Illumina Genome Analyzer II
Description
Rift Valley Fever Virus (RVFV), a negative-stranded RNA virus, is the etiological agent of the vector-borne zoonotic disease, Rift Valley Fever (RVF). In both humans and livestock, protective immunity can be achieved through vaccination. Earlier and more recent vaccine trials in cattle and sheep demonstrated a strong neutralizing antibody and total IgG response induced by the RVFV vaccine, MP-12. From previous work, protective immunity in sheep and cattle vaccinates normally occurs from 7 to 21 days after inoculation with MP-12. While the serology and protective response induced by MP-12 has been studied, little attention has been paid to the underlying molecular and genetic events occurring prior to the serologic immune response. To address this, we isolated RNA from whole blood from vaccinates over a time course of 21 days before and after inoculation during a recent vaccine trial with MP-12. This RNA time course was deeply sequenced by RNASeq and bioinformatically analyzed. Our results revealed time-dependent activation or repression of numerous gene ontologies and pathways related to immune response and regulation. Additional analyses identified a correlative relationship between specific genes related to immune activity and protective immunity prior to serologic detection of antibody response. These data provide an important proof of concept for identifying molecular and genetic components underlying the immune response to vaccination and protection prior to serologic detection. Overall design: Experimental Animals: Healthy, 4 – 6 month old Bos taurus heifer and steer calves were used in the present study. The calves were seronegative to both bovine viral diarrhea and bovine leukemia virus by antigen capture enzyme-linked immunosorbent assay (ELISA) analyses done at the Texas Veterinary Medical Diagnostic Laboratory, College Station, Texas and had no detectable neutralizing antibodies to RVFV by PRNT80 at the time of vaccination. The animal experiments were performed under an Institutional Animal Care and Use Committee approved protocol #2010-192. Vaccines: The authentic recombinant MP-12 (MP12) is an attenuated RVFV vaccine prepared for use in humans by the U. S. Army Medical Research Institute of Infectious Diseases. Vaccines were propagated and prepared at University of Texas Medical Branch in Galveston, TX. Experimental Design: The calves were housed in an ABSL2 Ag biocontainment facility where they were randomized into test groups and acclimated to the facility for 14 days. Animals were inoculated either subcutaneously (s.c.) or intramuscularly (i.m.) with 1x105 PFU of MP-12 (3 animals in each group). Whole blood was collected prior to inoculation on Days 0 through 7, 10, 14, 21 and preserved for serum neutralization studies (PRNT) or total RNA purification for RNASeq analysis. Experimentally determined PRNT values were used to determine the “serologic response status” for animals “unvaccinated”, “vaccinated, not protected”, or “vaccinated, protected” with animals having a serum dilution ration of >1:80 being considered protected. Only RNA samples that met the minimum quality and quantity thresholds were used for the sequencing analysis. Rectal temperatures were recorded each time blood was collected and their health status was documented daily. At the end of the respective studies, the calves were euthanized with pentobarbital sodium (120 mg/kg i.v.). All calves were healthy and clinically normal at the termination of the respective studies. Morrill, John C., Richard C. Laughlin, Nandadeva Lokugamage, Jing Wu, Roberta Pugh, Pooja Kanani, L. Garry Adams, Shinji Makino, C. J. Peters. Immunogenicity of a Recombinant Rift Valley Fever MP-12 Vaccine Candidate in Calves. Vaccine. 2013. doi:10.1016/j.vaccine.2013.08.003. 238. Morrill, John C., Richard C. Laughlin, Nandadeva Lokugamage, Roberta Pugh, Elena Sbrana, William J. Weise, L. Garry Adams, Shinji Makino and C. J. Peters.. Safety and Immunogenicity of Recombinant Rift Valley Fever MP-12 Vaccine Candidates in Sheep. Vaccine 10.1016/j.vaccine.2012.10.118, 2012.
Publication Title
Correlative Gene Expression to Protective Seroconversion in Rift Valley Fever Vaccinates.
Sample Metadata Fields
Specimen part, Subject, Time
View Samples- Mus musculus
- 6 Downloadable Samples
Affymetrix Mouse Gene 2.0 ST Array (mogene20st)
Description
Fzd2 is a Wnt receptor expressed in the embryonic lung. We made a conditional knockout of Fzd2 to specifically address the role of signaling through Fzd2 in lung epithelial development.
Publication Title
Wnt ligand/Frizzled 2 receptor signaling regulates tube shape and branch-point formation in the lung through control of epithelial cell shape.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 8 Downloadable Samples
- Affymetrix Mouse Gene 2.0 ST Array (mogene20st)
Description
Ezh2 epigenetically suppresses developmentally-regulated genes. Ezh2 is highly expressed during development, including in the lung. We knocked out Ezh2 in the developing lung epithelium using a Shh-cre driver which is active in foregut endoderm prior to lung morphogenesis. Many developmentally regulated genes became derepressed in the mutant lungs, leading to defects in lung development.
Publication Title
Ezh2 represses the basal cell lineage during lung endoderm development.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Gene 2.0 ST Array (mogene20st)
Description
To identify potential biological functions for three lncRNAs (NANCI, LL12, and LL34) we used shRNAs to knockdown expression of lncRNAs in MLE12 cells, a cell resembling type two lung epithelial cells. This data set contains the microarrays looking at gene expression.
Publication Title
Long noncoding RNAs are spatially correlated with transcription factors and regulate lung development.
Sample Metadata Fields
Treatment
View Samples- Mus musculus
- 10 Downloadable Samples
- Affymetrix Mouse Gene 2.0 ST Array (mogene20st)
Description
The molecular mechanism of how lung sacculation occurs is poorly understood. Loss of epithelial Hdac3 results in defects in the proper expansion of distal lung saccules into primitive alveoli. In this microarray, we seek to investigate the gene profile changes caused by loss of Hdac3 to better understand the molecular pathways that are regulated by Hdac3 during lung sacculation.
Publication Title
HDAC3-Dependent Epigenetic Pathway Controls Lung Alveolar Epithelial Cell Remodeling and Spreading via miR-17-92 and TGF-β Signaling Regulation.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 22 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Sox17 expression confers self-renewal potential and fetal stem cell characteristics upon adult hematopoietic progenitors.
Sample Metadata Fields
Age, Specimen part, Treatment
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
The transcription factor SOX17 is expressed by fetal, but not adult hematoipoietic stem cells (HSCs), and is required for the maintenance of fetal and neonatal, but not adult, HSCs. In the current study we show that ectopic expression of Sox17 in adult HSCs and transiently reconstituting multipotent progenitors was sufficient to confer increased self-renewal potential and the expression of fetal HSC genes including fetal HSC surface markers.
Publication Title
Sox17 expression confers self-renewal potential and fetal stem cell characteristics upon adult hematopoietic progenitors.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Mus musculus
- 10 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
The transcription factor SOX17 is expressed by fetal, but not adult hematoipoietic stem cells (HSCs), and is required for the maintenance of fetal and neonatal, but not adult, HSCs. In the current study we show that ectopic expression of Sox17 in adult HSCs and transiently reconstituting multipotent progenitors was sufficient to confer increased self-renewal potential and the expression of fetal HSC genes including fetal HSC surface markers.
Publication Title
Sox17 expression confers self-renewal potential and fetal stem cell characteristics upon adult hematopoietic progenitors.
Sample Metadata Fields
Age, Specimen part, Treatment
View Samples- Saccharomyces cerevisiae
- 10 Downloadable Samples
- Illumina HiSeq 2000
Description
Purpose: Understand the synergistic relationship between the methyltransferases Set1 and Set5 in the regulation of gene expression. Methods: Total mRNA was obtained from two independent biological replicates each of wildtype (WT), set1?, set5?, SET5 Y402A and set1?set5? S. cerevisiae strains. Libraries were generated and sequenced using an Illumina HiSeq2000 platform. The sequence reads that passed quality filters were mapped using TopHat and expression levels were quantified using Cufflinks. Results: We generated FPKM expression values for each transcript and identified the differentially expressed genes using an FDR-adjusted p-value of 0.05. Subsequent data analysis was restricted to genes with fold-change greater than 1.7 relative to WT. Our results show that Set1 and Set5 have roles primarily in transcription repression. Moreover, lack of both Set1 and Set5 results in a synergistic exhacerbation of the transcriptional derepression observed in the single mutants. Further analysis revealed a specific enrichment of the Set5/Set1-repressed genes near repetitive DNA sequences of the genome. Conclusions: Our study uncovers an unexpected synergistic role of Set1 and Set5 in transcription repression of telomeric regions and Ty retrotransposons. Overall design: mRNA profiles of wildtype (WT), set1?, set5?, SET5 Y402A and set1?set5? were generated by sequencing using an Illumina HiSeq2000 platform. Two biological replicates of each strain were used.
Publication Title
Transcriptome profiling of Set5 and Set1 methyltransferases: Tools for visualization of gene expression.
Sample Metadata Fields
Cell line, Subject
View Samples- Mus musculus
- 9 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
As Prdm16 deficiency reduces self-renewal potential and depletes neural stem cells in culture we decided to investigate the underlying molecular mechanisms of the neural stem cells depletion in the Prdm16 deficient animals. For the experiment we used Prdm16Gt(OST67423)Lex (Prdm16LacZ) genetrap mice obtained from the NIH Mutant Mouse Regional Resource Center (http://www.mmrrc.org/).
Publication Title
Prdm16 promotes stem cell maintenance in multiple tissues, partly by regulating oxidative stress.
Sample Metadata Fields
Specimen part
View Samples