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Mus musculus
2 Downloadable Samples
Illumina HiSeq 2500
Description
Multiple signaling pathways, structural proteins and transcription factors are involved in regulation of endothelial barrier function. The Forkhead protein FOXF1 is a key transcriptional regulator of lung embryonic development, and we use a conditional knockout approach to examine the role of FOXF1 in adult lung homeostasis and lung injury and repair. Tamoxifen-regulated deletion of both Foxf1 alleles in endothelial cells of adult mice (Pdgfb-iCreER/Foxf1 caused lung inflammation and edema, leading to respiratory insuffency and uniform mortality. Deletion of a single foxf1 allele was sufficient to increase susceptibility of heterozygous mice to acute lung injury. FOXF1 abundance was decreased in pulmonary endothelial cells of human patients with acute lung injury. Gene expression analysis of pulmonary endothelial cells of FOXF1 deletion indicated reduced expression for genes critical for maintance and regulation of adherens junctions. FOXF1 knockdown in vitro and in vivo disrupted adherens junctions, increased lung endothelial permeability, and the abundance of mRNA and protein for sphingosine 1 phosphate receptor 1 (S1PR1), a key regulator of endothelial barrier function. Chromatin immunoprecipitation and luciferase reporter assay demonstrated that FOXF1 directly bound to and induced the tanscriptional activity of the S1pr1 promoter. Pharmacological administratiion of S1P to injured pdgfb-iCreER/Foxf1 mice restored endothelial barrier function, decreased lung edema and improved survival. Thus, FOXF1 promotes normal lung homeostasis and lung repair, at least in part, by enhancing endothelial barrier function through transcriptional activation of the S1P/S1PR1/ signaling pathway. Overall design: RNA was isolated and pooled from the lungs of multiple mice with either the Foxf1 floxed alleles alone or Pdgfb-iCreER Foxf1 floxed mice.
Publication Title
FOXF1 maintains endothelial barrier function and prevents edema after lung injury.
Sample Metadata Fields
Specimen part, Subject
View Samples- Mus musculus
- 2 Downloadable Samples
- Illumina HiSeq 2000
Description
Hepatic fibrosis is the common end stage to a variety of chronic liver injuries and is characterized by an excessive deposition of extracellular matrix (ECM), which disrupts the liver architecture and impairs liver function. The fibrous lesions are produced by myofibroblasts, which differentiate from hepatic stellate cells (HSC). The myofibroblasts transcriptional networks remain poorly characterized. Previous studies have shown that the Forkhead box F1 (FOXF1) transcription factor is expressed in HSCs and stimulates their activation during acute liver injury; however, the role of FOXF1 in the progression of hepatic fibrosis is unknown. In the present study, we generated aSMACreER;Foxf1fl/fl mice to conditionally inactivate Foxf1 in myofibroblasts during carbon tetrachloride-mediated liver fibrosis. Foxf1 deletion increased collagen depositions and disrupted liver architecture. Timp2 expression was significantly increased in Foxf1-deficient mice while MMP9 activity was reduced. RNA sequencing of purified liver myofibroblasts demonstrated that FOXF1 inhibits expression of pro-fibrotic genes, Col1a2, Col5a2, and Mmp2 in fibrotic livers and binds to active repressors located in promotors and introns of these genes. Overexpression of FOXF1 inhibits Col1a2, Col5a2, and MMP2 in primary murine HSCs in vitro. Altogether, FOXF1 prevents aberrant ECM depositions during hepatic fibrosis by repressing pro-fibrotic gene transcription in myofibroblasts and HSCs. Overall design: RNAseq on isolated hepatic stromal cells from Foxf1 fl/fl and aSMACreER;Foxf1 fl/fl mice after 5 weeks of carbon tetrachloride-induced liver injury.
Publication Title
The Forkhead box F1 transcription factor inhibits collagen deposition and accumulation of myofibroblasts during liver fibrosis.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Homo sapiens
- 51 Downloadable Samples
- Illumina HiSeq 4000, NextSeq 500
Description
We describe the viral gene expression cascade at the single-cell level, showing bifurcations and bottleneck states. Host gene expression changes are related to viral transcription. The role of cellular signaling pathways in infection is studied using trajectory analysis and the importance of the Nrf2 transcription factor studied in follow-up experiments. Overall design: Human primary fibroblasts were infected with HSV-1 and single-cell RNA-sequencing was performed at different early time points after infection.
Publication Title
Single-cell RNA-sequencing of herpes simplex virus 1-infected cells connects NRF2 activation to an antiviral program.
Sample Metadata Fields
Subject
View Samples- Triticum aestivum
- 35 Downloadable Samples
Affymetrix Wheat Genome Array (wheat)
Description
The wheat gene Lr34 confers partial resistance to all races of Puccinia triticina, the causal agent of wheat leaf rust. However, the biological basis for the exceptional durability of Lr34 is unclear. The Affymetrix wheat genome array was used to identify wheat genes differentially expressed in a compatible interaction (Tc), an R-gene mediated incompatible interaction (Tc-Lr1), and a race non-specific resistance interaction (Tc-Lr34) in response to infection challenge by P. triticina race 1 at anthesis. Transcriptome interrogation was conducted by comparing mock- and P. triticina-inoculated leaves harvested at 3 and 7 days post inoculation (dpi).
Publication Title
Lr34-mediated leaf rust resistance in wheat: transcript profiling reveals a high energetic demand supported by transient recruitment of multiple metabolic pathways.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 6 Downloadable Samples
- Illumina MouseWG-6 v2.0 expression beadchip
Description
Chronic loss of Lasp1 alters the expression of other genes associated with cell motility/attachment, and/or other cellular functions. Results provide new information showing that loss of Lasp1 leads to up- and down-regulation of genes involved in cell motility/attachment/growth.
Publication Title
Lasp1 gene disruption is linked to enhanced cell migration and tumor formation.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 4 Downloadable Samples
- Illumina HiSeq 2000
Description
The T-box transcription factor TBX18 is essential to mesenchymal cell differentiation in several tissues and Tbx18 loss-of-function results in dramatic organ malformations and perinatal lethality. Here we demonstrate for the first time that Tbx18 is required for the normal development of periductal smooth muscle stromal cells in prostate, particularly in the anterior lobe, with a clear impact on prostate health in adult mice. Prostate abnormalities are only subtly apparent in Tbx18 mutants at birth; to examine postnatal prostate development we utilized a relatively long-lived hypomorphic mutant and a novel conditional Tbx18 allele. Similar to the ureter, cells that fail to express Tbx18 do not condense normally into smooth muscle cells of the periductal prostatic stroma. However, in contrast to ureter, the periductal stromal cells in mutant prostate assume a hypertrophic, myofibroblastic state and the adjacent epithelium becomes grossly disorganized. To identify molecular events preceding the onset of this pathology, we compared gene expression in the urogenital sinus (UGS), from which the prostate develops, in Tbx18-null and wild type littermates at two embryonic stages. Genes that regulate cell proliferation, smooth muscle differentiation, prostate epithelium development, and inflammatory response were significantly dysregulated in the mutant urogenital sinus around the time that Tbx18 is first expressed in the wild type UGS, suggesting a direct role in regulating those genes. Together, these results argue that Tbx18 is essential to the differentiation and maintenance of the prostate periurethral mesenchyme and that it indirectly regulates epithelial differentiation through control of stromal-epithelial signaling. Overall design: Embryos were collected from timed matings of Tbx18Gfp/+ knock-in mutants at E16.5 and E18.5, and genotyped to identify Tbx18Gfp/Gfp null mutants and wild-type (WT) littermates. The urogenital sinus (UGS) was dissected and used to extract RNA from each of three animals of each genotype. The RNA samples were pooled to generate libraries for sequencing.
Publication Title
Tbx18 Regulates the Differentiation of Periductal Smooth Muscle Stroma and the Maintenance of Epithelial Integrity in the Prostate.
Sample Metadata Fields
Specimen part, Subject
View Samples- Mus musculus
- 61 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
NOD mice were injected once a week with LTBR-Ig to block the LTBR-pathway, or with control monoclonal antibody MOPC from age 8 to 16 weeks old. Extraorbital lacrimal glands or submaxillary glands were dissected and total mRNA prepared. Each sample was either the combined lacrimals (2) from each mouse or individual salivary glands. There were 4 mice in each treatment group. Total mRNA was isolated and the quality was assessed using the Agilent 2100 Bioanalyzer (Agilent Technologies, Palo Alto, CA). Reverse transcription to prepare cDNA was performed using Invitrogen M-MLV system. The purpose was to determine changes in gene expression in glands due to blockade of the LTBR-pathway.
Publication Title
Lymphotoxin-beta receptor blockade reduces CXCL13 in lacrimal glands and improves corneal integrity in the NOD model of Sjögren's syndrome.
Sample Metadata Fields
Specimen part, Treatment, Time
View Samples- Homo sapiens
- 24 Downloadable Samples
- Affymetrix Human Transcriptome Array 2.0 (hta20)
Description
In an effort to define unique and common signatures of NK cell activity that is non-detected at the protein level, we studied the entire transcriptome of NK cells.
Publication Title
Transcriptomic signatures of NK cells suggest impaired responsiveness in HIV-1 infection and increased activity post-vaccination.
Sample Metadata Fields
Specimen part, Treatment, Subject
View Samples
GSE10801- Arabidopsis thaliana
- 6 Downloadable Samples
- Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)
Description
Heterologous expression of the fungal pathogen Cladosporium fulvum Avr2 in Arabidopsis plants.
Publication Title
The Cladosporium fulvum virulence protein Avr2 inhibits host proteases required for basal defense.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 4 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Loss of Rb family in HSC results in their sustained proliferation, impaired homeostasis and extramedullar mobility.
Publication Title
Rb family proteins enforce the homeostasis of quiescent hematopoietic stem cells by repressing Socs3 expression.
Sample Metadata Fields
Specimen part
View Samples