We report the correlation between lung-derived neonatal MSCs and 2 clinical variables among preterm newborns: corrected gestational age (CGA) at collection and the severity of bronchopulmonary dysplasia (BPD) Overall design: To test the correlation between the transcriptional profiles of tracheal aspirate-derived mesenchymal stromal cells with late stage lung development and with bronchopulmonary dysplasia.
Lung-Resident Mesenchymal Stromal Cells Reveal Transcriptional Dynamics of Lung Development in Preterm Infants.
Specimen part, Subject
View SamplesAIRmax and AIRmin mouse lines show a differential lung inflammatory response and differential lung tumor susceptibility after urethane treatment, thus constituting a good genetic model to investigate differences in gene expression profiles related to inflammatory response and lung tumor susceptibility. The transcript profile of ~24,000 known genes was analyzed in normal lung tissue of untreated and urethane-treated AIRmax and AIRmin mice. In lungs of untreated mice, inflammation associated genes involved in pathways such as leukocyte transendothelial migration, cell adhesion and tight junctions were differentially expressed in AIRmax versus AIRmin mice. Moreover, gene expression levels differed significantly in urethane-treated mice even at 21 days after treatment. In AIRmin mice, modulation of expression of genes involved in pathways associated with inflammatory response paralleled the previously observed persistent infiltration of inflammatory cells in the lung of these mice. In conclusion, a specific gene expression profile in normal lung tissue is associated with mouse line susceptibility or resistance to lung tumorigenesis and with different inflammatory response, and urethane treatment causes a long-lasting alteration of the lung gene expression profile that correlates with persistent inflammatory response of AIRmin mice.
Transcriptome of normal lung distinguishes mouse lines with different susceptibility to inflammation and to lung tumorigenesis.
Sex, Specimen part
View SamplesAmyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by progressive weakness from loss of motor neurons. The fundamental pathogenic mechanisms are unknown and recent evidence is implicating a significant role for abnormal exon splicing and RNA processing. Using new comprehensive genomic technologies, we studied exon splicing directly in 12 sporadic ALS and 10 control lumbar spinal cords acquired by a rapid autopsy system that processed nervous systems specifically for genomic studies. ALS patients had rostral onset and caudally advancing disease and abundant residual motor neurons in this region. We created two RNA pools, one from motor neurons collected by laser capture microdissection and one from the surrounding anterior horns. From each, we isolated RNA, amplified mRNA, profiled whole-genome exon splicing, and applied advanced bioinformatics. We employed rigorous quality control measures at all steps and validated findings by qPCR. In the motor neuron enriched mRNA pool, we found two distinct cohorts of mRNA signals, most of which were up-regulated: 148 differentially expressed genes (p103) and 411 aberrantly spliced genes (p105). The aberrantly spliced genes were highly enriched in cell adhesion (p1057), especially cell-matrix as opposed to cell-cell adhesion. Most of the enriching genes encode transmembrane or secreted as opposed to nuclear or cytoplasmic proteins. The differentially expressed genes were not biologically enriched. In the anterior horn enriched mRNA pool, we could not clearly identify mRNA signals or biological enrichment. These findings, perturbed and up-regulated cell-matrix adhesion, suggest possible mechanisms for the contiguously progressive nature of motor neuron degeneration.
Sporadic ALS has compartment-specific aberrant exon splicing and altered cell-matrix adhesion biology.
Sex, Age, Specimen part
View SamplesTo analyze the role of DNA methylation during differentiation, we performed genome-wide expression analysis of undifferentiated wild type, dnmt1-/- and triple knock out (TKO; dnmt1-/-, dnmt3a-/-, dnmt3b-/-) ESCs as well as respective embryoid bodies (EBs) at two stages of differentiation
Global DNA hypomethylation prevents consolidation of differentiation programs and allows reversion to the embryonic stem cell state.
Specimen part
View SamplesWe performed whole transcriptome profiling on sorted tissue macrophages from the spleen or from visceral adipose tissue (VAT) of wild-type mice that are 3-month or 24-month of age or from 24-month Nlrp3-/- mice Overall design: Profiles were generated on fluorescence-activated-cells (FACs) sorted F480+CD11b+ cells from spleen or adipose tissue, using sequencing analysis
Inflammasome-driven catecholamine catabolism in macrophages blunts lipolysis during ageing.
Sex, Age, Specimen part, Subject
View SamplesThe goal of this study was to determine the effects of a well-characterized anti-androgen, abiraterone acetate, and a suspected human anti-androgen, di-n-butyl phthalate (DBP) on the androgenic function of human fetal testis. Human fetal testis was xenografted into the renal subcapsular space of castrated male athymic nude mice. Hosts were treated with hCG to stimulate testosterone production in the xenografts, and were concurrently treated with either abiraterone acetate or DBP. While abiraterone acetate (14 d, 75 mg/kg/d p.o.) dramatically reduced testosterone and the weights of androgen-sensitive host organs, DBP (14 d, 500 mg/kg/d p.o.) had no effect on androgenic endpoints.
Differential response to abiraterone acetate and di-n-butyl phthalate in an androgen-sensitive human fetal testis xenograft bioassay.
Specimen part
View SamplesThe goal of this project is to generate transcriptome profiling of intestinal stem cells for a systemic analysis of cellular pathways involved in responses to fasting. Overall design: Examination of one cell type in two conditions.
Fasting Activates Fatty Acid Oxidation to Enhance Intestinal Stem Cell Function during Homeostasis and Aging.
Age, Specimen part, Cell line, Subject
View SamplesPurpose:The goals of this study was to determine alterations in expression levels of transcripts downstream of a dominant-negative transcription factor. Quantitative reverse transcription polymerase chain reaction (qRT–PCR) methods was used to confirm the altered expression of targets. Methods: Striatal mRNA profiles of 11-month-old wild-type (WT) and Nestin-Cre X PPAR delta E411P mice were generated by deep sequencing, in triplicate, using Illumina HiSeq 2000. The sequence reads that passed quality filters were analyzed at the transcript isoform level with TopHat followed by Cufflinks. qRT–PCR validation was performed using TaqMan and SYBR Green assays. Western blots, and immunofluorescence was also used to confirm if altered mRNA levels translated to changes at the protein level. Results: Using data analysis workflow, we mapped sequence reads for each sample to the mouse genome (build mm9) and identified transcripts in the striatum of WT and PPARdelta E411P mice. Conclusions: Our study found multiple transcripts altered in the striatum of the Nestin-Cre x PPAR delta E411P mice as compared to WT striatum, as generated by RNA-SEQ in biologic replicates. Overall design: Striatal mRNA profiles of 11-month-old wild type (WT) and Nestin-Cre X PPAR delta E411P mice were generated by deep sequencing, in triplicate, using Illumina HiSeq2000.
PPAR-δ is repressed in Huntington's disease, is required for normal neuronal function and can be targeted therapeutically.
Specimen part, Cell line, Subject
View SamplesGastrocnemius muscle biopsies were obtained from 15 health older adults without peripheral artery disease (PAD), 20 PAD patients with intermittent claudication, and 16 patients with critical limb ischemia undergoing limb amputation. Gene expression analysis was performed using RNA sequencing analysis. Overall design: Examination of gene expression differences across the clinical spectrum of PAD (healthy vs. claudicant vs. critical limb ischemia)
Extensive skeletal muscle cell mitochondriopathy distinguishes critical limb ischemia patients from claudicants.
Specimen part, Disease, Subject
View SamplesThe goal of this set of experiments was to identify transcripts that are differentially expressed upon reactivation of NMD in an nmd2::HIS3 strain by galactose-induced expression of the NMD2 gene.
Association of yeast Upf1p with direct substrates of the NMD pathway.
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