Background: Kawasaki Disease (KD) is a childhood illness of suspected infectious etiology that causes medium-sized muscular arteritis, most critically affecting the coronary arteries. No single diagnostic test exists, hampering early diagnosis and treatment. Approximately 25% of untreated patients develop coronary artery disease, and children who are treated with intravenous gammaglobulin but do not respond are also at high risk. Subacute/chronic arteritis and luminal myofibroblastic proliferation are the pathologic processes occurring in KD CA after the second week of illness, when neutrophilic necrotizing arteritis has subsided. The specific dysregulated immune pathways contributing to subacute/chronic arteritis have been unknown, hampering the development of effective immunomodulatory therapies for patients not responding to intravenous gammaglobulin therapy. Methods and Results: Deep RNA sequencing was performed on KD (n=8) and childhood control (n=7) coronary artery tissues, revealing 1074 differentially expressed mRNAs. Molecular pathways involving T helper cell, cytotoxic T lymphocyte, dendritic cells, and antigen presentation were the most significantly dysregulated. There was significant upregulation of immunoglobulin and type I interferon-stimulated genes. 80 upregulated extracellular genes encoding secreted proteins are candidate biomarkers of KD arteritis. Conclusions: The immune transcriptional profile in KD coronary artery tissues is primarily T helper and cytotoxic lymphocyte-mediated, and has features of an antiviral immune response such as type I interferon-stimulated gene expression. This first report of the KD coronary artery transcriptome identifies specific dysregulated immune response pathways that can inform the development of new therapies for and biomarkers of KD arteritis, and provide direction for future etiologic studies. Overall design: Primary analysis: 8 KD coronary arteries versus 7 childhood control coronary arteries. Subanalysis 1: 4 untreated KD coronary arteries versus 7 childhood control coronary arteries and subanalysis 2: 4 treated KD coronary arteries versus 7 childhood control coronary arteries
The transcriptional profile of coronary arteritis in Kawasaki disease.
No sample metadata fields
View SamplesThe goal of the study was to analyze the principles governing the usage of alternatively spliced transcript isoform of four types of T-cells (Naïve, Central Memory, Transitional Memory and Effector Memory) between resting and activated status. However, the principles discovered in the T cells were universal and can also be applied to other cell type and tissues. Overall design: Four types of T cells were sorted and whole transcriptome analysis was performed using an Illumina machine The readme.txt contains the column headers and description for the processed data files.
Stochastic principles governing alternative splicing of RNA.
Subject
View SamplesRNAs were isolated from FACS sorted ScxGFP positive cells of hindlimbs at E11.5, E13.5 and E15.5, and characterized by RNAseq Overall design: 18 hindlimbs, 12 hindlimbs and 11 hindlimbs were pooled together for E11.5, E13.5 and E15.5, respectively.GFP positive cells were FACS sorted, then for RNA extraction, cDNA library preparation and proceeded for RNAseq
Whole transcriptome expression profiling of mouse limb tendon development by using RNA-seq.
No sample metadata fields
View SamplesRNAs were isolated from FACS sorted ScxGFP positive cells and GFP negative cells of forelimbs at E13.5, and characterized by RNAseq Overall design: for each sample, 3 pairs of total 6 E13.5 forelimbs were pooled together, both GFP positive cells and GFP negative cells were FACS sorted, then for RNA extraction, cDNA library preparation and proceeded for RNAseq
Whole transcriptome expression profiling of mouse limb tendon development by using RNA-seq.
No sample metadata fields
View SamplesAnalysis of the roles of Irx3 and Irx5 transcription factors in mouse heart development and postnatal heart function. Results show that show that Irx3 and Irx5 have redundant function in the in the endocardium to regulate atrioventricular canal morphogenesis and outflow tract formation. A postnatal deletion of Irx3 and Irx5 surprisingly results in a restoration of the repolarization gradient that is altered in Irx5 mutant hearts, suggesting a model whereby postnatal Irx3 activity is normally repressed by Irx5.
Cooperative and antagonistic roles for Irx3 and Irx5 in cardiac morphogenesis and postnatal physiology.
Specimen part
View SamplesThe 5HT system is organized into rostral and caudal populations with discrete anatomical locations and opposite axonal trajectories in the developing hindbrain. 5HT neuron cell bodies in the rostral subdivision migrate to the midbrain and pons and extend ascending projections throughout the forebrain. 5HT cell bodies in the caudal subdivision migrate to the ventral medulla and caudal half of the pons and provide descending projections to the brainstem and spinal cord.
Distinct transcriptomes define rostral and caudal serotonin neurons.
Specimen part
View SamplesSolid cancers develop within a supportive microenvironment that promotes tumor formation and continued growth through the elaboration of mitogens and chemokines. Within these tumors, monocytes (macrophages and microglia) represent rich sources of these stromal factors. Leveraging a genetically-engineered mouse model of neurofibromatosis type 1 (NF1) low-grade brain tumor (optic glioma), previous studies have demonstrated that microglia are important for glioma formation and maintenance. To identify the tumor-associated microglial factors that support glioma growth (gliomagens), we employed a comprehensive large scale discovery effort using optimized advanced RNA-sequencing methods. Candidate gliomagens were prioritized to identify potential secreted or membrane-bound proteins, which were next validated by quantitative RT-PCR and RNA FISH following minocycline-mediated microglial inactivation in vivo. Using these selection criteria, Ccl5 was identified as a highly expressed chemokine in both genetically engineered Nf1 mouse and human optic gliomas. As a candidate gliomagen, recombinant Ccl5 increased Nf1-deficient optic nerve astrocyte growth in vitro. Importantly, consistent with its critical role in maintaining tumor growth, Ccl5 inhibition with neutralizing antibodies reduced Nf1 mouse optic glioma growth in vivo. Collectively, these findings establish Ccl5 as critical stromal growth factor in low-grade glioma maintenance relevant to future microglia-targeted therapies for brain tumors. Overall design: Nf1 optic glioma associated microglia from mice were flow sorted. Upregulated genes of glioma associated microglia were verified and further examined.
RNA Sequencing of Tumor-Associated Microglia Reveals Ccl5 as a Stromal Chemokine Critical for Neurofibromatosis-1 Glioma Growth.
No sample metadata fields
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Genomic impact of transient low-dose decitabine treatment on primary AML cells.
Sex, Age, Specimen part, Disease, Treatment
View SamplesAcute myeloid leukemia (AML), and other myeloid malignancies, are frequently treated with hypomethylating agents like decitabine. Alterations in the epigenome, induced by decitabine, are likely to result in gene expression changes. The effects of decitabine have not been systemically studied using primary AML samples.
Genomic impact of transient low-dose decitabine treatment on primary AML cells.
Specimen part, Disease, Treatment
View SamplesWe interrogated the transcriptome using RNA-seq at several stages of an mouse embryonic stem cell to cardiomyocyte directed differentiation protocol. These four stages represent timepoints when differentiating cultures are enriched for embryonic stem cells (ESC), mesodermal cells (MES), cardiac precursors (CP), or cardiomyocytes (CM) respectively. This study revealed many dynamic patterns of mRNAs and long non-coding RNAs (lncRNAs) and identified groups of genes with similar expression patterns during differentiation. Overall design: RNA-seq analysis of global RNA levels at 4 stages of directed cardiac differentiation of mouse embryonic stem cells. Each stage in biological duplicates
Dynamic and coordinated epigenetic regulation of developmental transitions in the cardiac lineage.
Specimen part, Cell line, Subject, Time
View Samples