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SRP061376
Mus musculus
9 Downloadable Samples
Illumina HiSeq 2000
Description
Arterial occlusive diseases are major causes of morbidity and mortality. Blood flow to the affected tissue must be restored quickly if viability and function are to be preserved. Collaterals are artery-to-artery or arteriole-to-arteriole interconnections that can bypass an occlusion by providing an alternative route for blood flow to the affected tissue. The increased flow and sheer stress initiate processes that result in the remodeling (arteriogenesis) of these vessels into efficient conductance arteries. Here we report that the mixed-lineage kinase (MLK) pathway activates cJun NH2-terminal kinase (JNK) in endothelial cells. Disruption of Mlk2/3 or Jnk1/2 genes caused severe blockade of blood flow and failure to recover in the femoral artery ligation model of hindlimb ischemia because of abnormal collateral arteries. We show that the MLK-JNK pathway is essential for patterning and maturation of collateral arteries during development, but this pathway is not required for angiogenesis or arteriogenesis in adults. JNK in endothelial cells promotes Delta-like 4-induced Notch signaling and suppresses excessive sprouting angiogenesis during development. This function of the MLK-JNK pathway contributes to normal formation of native collateral arteries. The MLK-JNK pathway is therefore a key regulatory mechanism for vascular development. These data highlight the crucial importance of the collateral circulation in the response to arterial occlusive diseases. Overall design: RNA-seq analysis of mouse lung endothelial cells (MLEC) of the following genotypes Cdh5-Cre+ Jnk1+/+ Jnk2+/+ Jnk3-/-(ECtrl), Cdh5-Cre- Jnk1LoxP/LoxP Jnk2LoxP/LoxP Jnk3-/- (EfCtrl), and Cdh5-Cre+ Jnk1LoxP/LoxP Jnk2LoxP/LoxP Jnk3-/- (E3KO). Three separate samples from mouse lung endothelial cells of each genotype were analyzed.
Publication Title
Suppression of ischemia in arterial occlusive disease by JNK-promoted native collateral artery development.
Sample Metadata Fields
No sample metadata fields
View Samples- Saccharomyces cerevisiae
- 8 Downloadable Samples
Affymetrix Yeast Genome S98 Array (ygs98)
Description
We addressed changes in gene expression profile in response to
Publication Title
Role of PUG1 in inducible porphyrin and heme transport in Saccharomyces cerevisiae.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 30 Downloadable Samples
- NextSeq 500
Description
Development requires the cooperation of tissue-specific and ubiquitously expressed transcription factors, such as Sp-family members. However, the molecular details of how ubiquitous factors participate in developmental processes are still unclear. We previously showed that during the differentiation of embryonic stem cells lacking Sp1 DNA binding activity (Sp1deltaDBD/deltaDBD cells), early blood progenitors are formed. However, gene expression during differentiation becomes progressively deregulated and terminal differentiation is severely compromised. Here we studied the cooperation of Sp1 and its closest paralogue Sp3 in hematopoietic development and demonstrate that Sp1 and Sp3 binding sites largely overlap. Sp3 cooperates with Sp1deltaDBD/deltaDBD but is unable to support hematopoiesis in the complete absence of Sp1. Using single cell gene expression analysis, we show that the lack of Sp1 DNA binding leads to a distortion of cell fate decision timing, indicating that stable chromatin bi nding of Sp1 is required to maintain robust differentiation trajectories. Overall design: RNA-Seq in ESC, Flk, HE1, HE2 and progenitor cells with WT, Sp1deltaDBD or Sp3KO
Publication Title
Robust hematopoietic specification requires the ubiquitous Sp1 and Sp3 transcription factors.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Mus musculus
- 2 Downloadable Samples
- NextSeq 500
Description
Development requires the cooperation of tissue-specifically and ubiquitously expressed transcription factors, such as Sp-family members. However, the molecular details of how ubiquitous factors participate in developmental processes are still unclear. We previously showed that during the differentiation of embryonic stem cells lacking Sp1 DNA binding activity (Sp1DDBD/DDBD cells), early blood progenitors are formed. However, gene expression during differentiation becomes progressively deregulated and terminal differentiation is blocked. Here we studied the cooperation of Sp1 and its homologue Sp3 in hematopoietic development and demonstrate that Sp1 and Sp3 binding sites largely overlap. Sp3 cooperates with Sp1DDBD/DDBD cells but is unable to support hematopoiesis in the complete absence of Sp1. Using single cell gene expression analysis, we show that the lack of Sp1 DNA binding leads to a distortion of cell fate decision timing, indicating that stable chromatin binding of Sp1 is required to maintain robust differentiation trajectories. Overall design: Chromium 10X - Single-cell RNA-seq of Sp1 wild-type and Sp1 DNA binding domain mutant cells
Publication Title
Robust hematopoietic specification requires the ubiquitous Sp1 and Sp3 transcription factors.
Sample Metadata Fields
Specimen part, Subject
View Samples- Danio rerio
- 2 Downloadable Samples
- IlluminaHiSeq2500
Description
A zebrafish forward genetic screen for determinants of susceptibility to Mycobacterium marinum identified a hypersusceptible mutant deficient in the lysosomal hydrolase Cathepsin L that manifests the hallmarks of human lysosomal storage diseases. In uninfected mutants, macrophages progressively accumulate undigested material in their lysosomes, leading to impaired migration and the accumulation of unengulfed cell debris. During mycobacterial infection, these vacuolated macrophages cannot migrate to phagocytose infected macrophages undergoing apoptosis in the tuberculous granuloma. Consequently, unengulfed apoptotic macrophages undergo secondary necrosis causing granuloma breakdown and increased mycobacterial growth. Macrophage lysosomal accumulations similarly impair migration to newly infecting mycobacteria. We find that important aspects of this phenotype are recapitulated in human smokers, who are at increased risk for tuberculosis. A majority of alveolar macrophages from smokers exhibit lysosomal accumulations and do not migrate to Mycobacterium tuberculosis. This incapacitation of highly microbicidal first-responding macrophages may contribute to smokers' susceptibility to tuberculosis. Overall design: A forward genetic screen for zebrafish larvae that are hypersusceptible to Mycobacterium marinum infection identified a mutation in the transcription factor snapc1b at 13: 37996163 (T->C). Individuals of wild type (T/T) and mutant (C/C) were genotyped and pooled respectively for RNA isolation and transcriptome analysis.
Publication Title
Lysosomal Disorders Drive Susceptibility to Tuberculosis by Compromising Macrophage Migration.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 2 Downloadable Samples
- Affymetrix Mouse Gene 2.0 ST Array (mogene20st)
Description
JNK3 deficiency leads to upregulation of growth factors such as Vegfa, Pdgfb, Pgf, Hbegf and Tgfb3 in ischemic muscle. In order to ascertain the molecular mechanisms responsible for the accelerated blood flow recovery in Mapk10-deficient mice, a micro-array analysis of gastrocnemius muscle from these mice was performed after HLI. We observed a significant up-regulation of several growth factors known to improve blood flow recovery in the Mapk10-/- muscle compared to WT
Publication Title
Neural JNK3 regulates blood flow recovery after hindlimb ischemia in mice via an Egr1/Creb1 axis.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 192 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
RNA was obtained from histologically normal bronchial epithelium of smokers during time of clinical bronchoscopy from relatively accessible airway tissue. Gene expression data from smokers with lung cancer was compared with samples from smokers without lung cancer. This allowed us to generate a diagnostic gene expression profile that could distinguish the two classes. This profile could provide additional clinical benefit in diagnosing cancer amongst smokers with suspect lung cancer.
Publication Title
Airway epithelial gene expression in the diagnostic evaluation of smokers with suspect lung cancer.
Sample Metadata Fields
Sex, Age, Race
View Samples- Mus musculus
- 6 Downloadable Samples
- Illumina MouseWG-6 v2.0 expression beadchip
Description
The purpose of this study was to identify putative downstream targets of the transcription factor ZIC2 in the mouse embryo. The results indicate loss of NODAL pathway expression, consistent with the observed phenotype of right isomerism in heart, lungs and viscera.
Publication Title
A Requirement for Zic2 in the Regulation of Nodal Expression Underlies the Establishment of Left-Sided Identity.
Sample Metadata Fields
Specimen part
View Samples- Drosophila melanogaster
- 10 Downloadable Samples
- Affymetrix Drosophila Genome Array (drosgenome1)
Description
The experiment was designed to identify genes abundant or enriched in adult Drosophila melanogaster Malpighian (renal) tubule as compared to the whole fly.
Publication Title
Function-informed transcriptome analysis of Drosophila renal tubule.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Drosophila melanogaster
- 10 Downloadable Samples
- Affymetrix Drosophila Genome Array (drosgenome1)
Description
This is an affymetrix array experiment comparing the transcriptome of the Malpighian tubule (or renal tubule) of 7-day adult Oregon R strain Drosophila melanogaster with matched whole fly samples.
Publication Title
Function-informed transcriptome analysis of Drosophila renal tubule.
Sample Metadata Fields
No sample metadata fields
View Samples