Asthma is a chronic inflammatory respiratory disease affecting over 300 million people around the world. Some asthma patients remain poorly controlled by conventional therapies and experience more life-threatening exacerbations. While patients with severe, refractory disease represent a heterogeneous group, a feature shared by most includes glucocorticoid insensitivity. We sought to characterize differences in the airway smooth muscle transcriptome response to glucocorticoids in fatal asthma vs. non-asthma donors. RNA-Seq was used to measure airway smooth muscle transcript expression differences between 9 donors with fatal asthma and 8 non-asthma donors. Cells from each donor were treated with budesonide or with vehicle control. Poly(A)-selected RNA-Seq libraries were prepared with the Illumina TruSeq method. An Illumina HiSeq 2500 instrument was used to generate 125 base pair paired-end reads. Overall design: Transcriptome profiles obtained via RNA-Seq for airway smooth muscle cells from 9 fatal asthma and 8 non-asthma donors treated with budesonide (100nM for 24h) or vehicle control were compared
Airway Smooth Muscle-Specific Transcriptomic Signatures of Glucocorticoid Exposure.
Specimen part, Disease, Disease stage, Treatment, Subject
View SamplesThe acute respiratory distress syndrome (ARDS) is a highly lethal syndrome characterized by hypoxemia and bilateral lung infiltrates in response to an inciting event such as sepsis. Allogeneic bone marrow transplantation (BMT) is a life-saving treatment for patients with hematologic malignancies that can be complicated by ARDS. We sought to identify blood gene expression signatures that distinguish whether ARDS in BMT may be a distinct pathobiologic entity from ARDS in non-BMT patients. RNA-Seq was used to measure whole blood transcript expression differences between 26 patients meeting the Berlin definition of ARDS: 8 patients without BMT and 5 BMT patients with ARDS from the Brigham and Women's Registry of Critical Illness (RoCI), as well as 7 non-BMT patients with sepsis and 6 BMT patients with sepsis. RNA was globin cleared using the Ambion GLOBINclear kit prior to preparation of poly(A)-selected RNA-Seq libraries with the Illumina TruSeq method. An Illumina HiSeq 2500 instrument was used to generate 75 base pair paired-end reads, which were aligned to the hg38 reference genome using STAR. Differential expression analysis was performed using DESeq2. Overall design: mRNA profiles obtained via RNA-Seq for whole blood samples from ARDS patients with and without BMT
Whole blood RNA sequencing reveals a unique transcriptomic profile in patients with ARDS following hematopoietic stem cell transplantation.
Specimen part, Disease, Subject
View SamplesContinuous stress caused by smoking induces changes in the cell population of small airway epithelium, with basal cell hyperplasia and goblet cell metaplasia at the expense of ciliated cells, and there is now compiling evidence that basal cells play a key role in the early pathogenesis of Chronic Obtructive Pulmonary Disease (COPD).
Microarray analysis identifies defects in regenerative and immune response pathways in COPD airway basal cells.
Specimen part, Disease stage
View SamplesRNAseq analysis was conducted to complement the targeted and untargeted metabolomics analysis of livers overexpressing the CoA-degrading enzyme Nudt7 or GFP (control). Lipid metabolism requires coenzyme A (CoA), which is found in multiple subcellular compartments including the peroxisomes. In the liver, CoA levels are dynamically adjusted between the fed and fasted states. The elevation in CoA levels that occurs during fasting is driven by increased synthesis but also correlates with decreased expression of Nudt7, the major CoA-degrading enzyme in the liver. Nudt7 resides in the peroxisomes and we overexpressed this enzyme in mouse livers to determine its effect on the size and composition of the hepatic CoA pool in the fed and fasted states. Nudt7 overexpression did not change total CoA levels but decreased the concentration of short-chain acyl-CoAs and choloyl-CoA in fasted livers, when endogenous Nudt7 activity was lowest. The effect on these acyl-CoAs correlated with a significant decrease in the hepatic bile acid content and in the rate of peroxisomal fatty acid oxidation, as estimated by targeted and untargeted metabolomics, combined with the measurement of fatty acid oxidation in intact hepatocytes. Identification of the CoA species and metabolic pathways affected the overexpression on Nudt7 in vivo supports the conclusion that the nutritionally-driven modulation of Nudt7 activity could contribute to the regulation of the peroxisomal CoA pool and peroxisomal lipid metabolism. Overall design: Liver mRNA profiles of 4 mice injected with adeno-associated virus to overexpress Nudt7 and 4 mice injected with adeno-associated virus to overexpress GFP (control) were generated by RNAseq using Illumina HiSeq1500
Overexpression of Nudt7 decreases bile acid levels and peroxisomal fatty acid oxidation in the liver.
Specimen part, Cell line, Subject
View SamplesInduction of dnFGFR2bfor 3 partially overlapping intervals at the early stages of otocyst morphogenesis revealed expected and novel up and downregulated genes that were validated by in situ hybridization analysis. Cell cyle genes were enriched in the downregulated datasets and human hearingloss genes were enriched in the upregulated datasets. Overall design: Differential mRNA expression analysis of pooled Rosa26rtTA/+ (control) and pooled Rosa26rtTA/+;Tg(tetO-s(dn)Fgfr2b)/+ (experimental) embryos induced with doxycycline for the indicated intervals. N=4 biological replicates per treatment (i.e. 4 pregnant females)
Spatial and temporal inhibition of FGFR2b ligands reveals continuous requirements and novel targets in mouse inner ear morphogenesis.
Subject
View SamplesA protocol was established for the derivation of Schwann cell-like cells from human BMSCs. The commitment to the Schwann cell fate was acquired by Schwann cell-like cells in co-culture with rat DRG neurons. Microarray analysis provided evidence that the human BMSC-derived Schwann cells were functionally mature.
Directed Differentiation of Human Bone Marrow Stromal Cells to Fate-Committed Schwann Cells.
Specimen part
View SamplesCcnyl1 is a newly identified genes, but the founction of which remained unclear, here we used the Ccnyl1 knockout mice to finding clues for its functional roles
CCNYL1, but Not CCNY, Cooperates with CDK16 to Regulate Spermatogenesis in Mouse.
Specimen part
View SamplesWe surveyed the transcriptomes of the whole heart and whole gastrocnemius muscle taken from two different types of Balb/c-DBAj hybrid mice (10-11 weeks old). The colon cancer bearing mice are called C26. The NTB are the non-tumor bearing mice.
Cardiac and skeletal muscles show molecularly distinct responses to cancer cachexia.
Specimen part
View SamplesThe goal of this study was to investigate the role of intragenic CTCF in alternative pre-mRNA splicing through a combined CTCF-ChIP-seq and RNA-seq approach. CTCF depletion led to decreased inclusion of weak upstream exons. Overall design: CTCF ChIP-seq was performed in BJAB and BL41 B cell lines and normalized relative to Rabbit Ig control IP-seq reads. RNA-seq was performed in BJAB and BL41 cells transduced with shRNA against CTCF or RFP as a control, and in untransduced cells as well.
CTCF-promoted RNA polymerase II pausing links DNA methylation to splicing.
Cell line, Subject
View SamplesCyclic AMP response element binding protein (CREB) is known to play important roles in growth and drug resistance of various cancers. Here we show roles of inhibition of CREB1 on gene expression profile of malignant mesothelioma (MM) cells (Hmeso and H2373/PPMMill).
CREB-induced inflammation is important for malignant mesothelioma growth.
Cell line
View Samples