Idiopathic pulmonary fibrosis (IPF) is associated with the accumulation of collagen-secreting fibroblasts and myofibroblasts in the lung parenchyma. Many mechanisms contribute to their accumulation, including resistance to apoptosis. In previous work, we showed that exposure to the pro-inflammatory cytokines, TNF- and IFN- reverses fibroblast resistance to apoptosis. The goal of this study was to investigate the underlying mechanism. Based on an initial interrogation of the transcriptomes of unstimulated and TNF- and IFN--stimulated primary lung fibroblasts and the lung fibroblast cell line, MRC5, we show here that among Fas-signaling pathway molecules, Fas expression was increased ~6-fold in an NF-B and p38mapk-dependent fashion. Prevention of the increase in Fas expression using Fas siRNAs blocked the ability of TNF- and IFN- to sensitize fibroblasts to Fas ligation induced-apoptosis; while enforced adenovirus-mediated Fas overexpression was sufficient to overcome basal resistance to Fas-induced apoptosis. Examination of lung tissues from IPF patients revealed low to absent staining of Fas in fibroblastic cells of fibroblast foci. Collectively, these findings suggest that increased expression of Fas is necessary and sufficient to overcome the resistance of lung fibroblasts to Fas-induced apoptosis. They also suggest that approaches aimed at increasing Fas expression by lung fibroblasts and myofibroblasts may be therapeutically relevant.
Increased cell surface Fas expression is necessary and sufficient to sensitize lung fibroblasts to Fas ligation-induced apoptosis: implications for fibroblast accumulation in idiopathic pulmonary fibrosis.
Specimen part, Treatment
View SamplesComparison between in vitro transcription- and cDNA-mediated annealing, selection and ligation (DASL)-based assays on brain-specific reference RNA, and postmortem frozen and formalin fixed brain tissue from autistic and control cases. Investigation of data preprocessing techniques for DASL-assayed RNA samples from frozen brain tissue.
Preprocessing and Quality Control Strategies for Illumina DASL Assay-Based Brain Gene Expression Studies with Semi-Degraded Samples.
Specimen part, Disease
View SamplesProper cortical development relies on the balance of neuronal migration and proliferation. We investigated the gene expression differences of mouse knock-outs for Lissencephaly in humans.
Global developmental gene expression and pathway analysis of normal brain development and mouse models of human neuronal migration defects.
Specimen part
View SamplesWe report RNA-Seq experiments of whole eye tissues from A/J, BALB/c, and C57BL/6 background mice. Overall design: Examine ocular tissue from 3 different background mice that display varying rates of retinal degeneration.
Transcriptome analysis reveals rod/cone photoreceptor specific signatures across mammalian retinas.
Sex, Age, Specimen part, Cell line, Subject
View SamplesWe report RNA-Seq experiments of eye and retinal tissues from WT and RHO KO mice Overall design: Examine ocular tissue from different mouse genotypes
Transcriptome analysis reveals rod/cone photoreceptor specific signatures across mammalian retinas.
Specimen part, Cell line, Subject
View SamplesWe report RNA-Seq experiments of whole eye tissues from C57BL/6J background mice at 1.5 h and 9.0 h after light onset to better understand photoreceptor phagocytosis Overall design: Examine ocular tissue from mice at different time points
Transcriptome analysis reveals rod/cone photoreceptor specific signatures across mammalian retinas.
Specimen part, Cell line, Subject, Time
View SamplesRIPK4 but not the related kinases RIPK1, RIPK2, and RIPK3 caused similar transcriptional changes to Wnt3a. Overall design: PA1 cells were transfected by 8ug RIPK1, RIPK2, RIPK3, or RIPK4 for 48h, RNA were extracted and sequenced.
Phosphorylation of Dishevelled by protein kinase RIPK4 regulates Wnt signaling.
Cell line, Subject
View SamplesHeterogeneity of meningeal cortical cells was deciphered on the molecular level using single cell RNA seq Overall design: RNA sequencing of 179 meningeal cortical cells isolated from naive wild-type mice
Neurogenic Radial Glia-like Cells in Meninges Migrate and Differentiate into Functionally Integrated Neurons in the Neonatal Cortex.
Sex, Specimen part, Subject
View SamplesIL-17 and TNF-alpha synergistically induce surface expression of IL-13Ra2 on primary lung fibroblasts, rendering them unresponsive to IL-13. Neutralizing antibodies to IL-13Ra2 restored IL-13-mediated signaling and transcriptome studies confirmed IL-13Ra2 is an IL-13 decoy receptor.
TNF-α/IL-17 synergy inhibits IL-13 bioactivity via IL-13Rα2 induction.
Specimen part, Cell line
View SamplesBackground: Septic shock heterogeneity has important implications for the conduct of clinical trials and individual patient management. We previously addressed this heterogeneity by indentifying 3 putative subclasses of children with septic shock based on a 100-gene expression signature corresponding to adaptive immunity and glucocorticoid receptor signaling. Herein we attempted to prospectively validate the existence of these gene expression-based subclasses in a validation cohort. Methods: Gene expression mosaics were generated from the 100 class-defining genes for 82 individual patients in the validation cohort. Patients were classified into 1 of 3 subclasses (A, B, or C) based on color and pattern similarity relative to reference mosaics generated from the original derivation cohort. Separate classifications were conducted by 21 individual clinicians and a computer-based algorithm. After subclassification the clinical database was mined for clinical phenotyping. Results: In the final consensus subclassification generated by clinicians, subclass A patients had a higher illness severity, as measured by illness severity scores and maximal organ failure, relative to subclasses B and C. The k coefficient across all possible inter-evaluator comparisons was 0.633. Similar observations were made based on the computer-generated subclassification. Patients in subclass A were also characterized by repression of a large number of genes having functional annotations related to zinc biology. Conclusions: We have validated the existence of subclasses of children with septic shock based on a biologically relevant, 100-gene expression signature. The subclasses can be indentified by clinicians without formal bioinformatics training, at a clinically relevant time point, and have clinically relevant phenotypic differences.
The influence of developmental age on the early transcriptomic response of children with septic shock.
Age, Specimen part, Disease, Disease stage
View Samples