The goal of this work was to identify all estrogen receptor beta target genes using RNA sequencing in MDA-MB-468 triple negative breast cancer cells engineered with inducible expression of full length estrogen receptor beta. Overall design: MDA-MB-468 breast cancer cells with inducible ERb expression (MDA-468-ERb cells) were treated in triplicate with vehicle (control, no ERb) or doxycycline (plus ERb) for 48 hr prior to treatment with 0.1% DMSO vehicle or 10 nM 17b-estradiol for 4 hr.
Research resource: global identification of estrogen receptor β target genes in triple negative breast cancer cells.
No sample metadata fields
View SamplesPP2A regulates inflammatory cytokine/chemokine gene expression by dephosphorylating protein kinases at multiple signaling pathways from stimulated cells. In this dataset, Affymetrix mouse Gene ST 2.1 Array was used to assay total RNA extracted from LPS-treated PP2AC knockout BMDM (PP2ACfl/fl;lyM-Cre) and the control BMDM (PP2ACfl/fl)
Myeloid-Specific Gene Deletion of Protein Phosphatase 2A Magnifies MyD88- and TRIF-Dependent Inflammation following Endotoxin Challenge.
Specimen part
View SamplesBackground: Septic shock is a heterogeneous syndrome within which probably exist several biological subclasses. Discovery and identification of septic shock subclasses could provide the foundation for the design of more specifically targeted therapies. Herein we tested the hypothesis that pediatric septic shock subclasses can be discovered through genome-wide expression profiling. Methods: Genome-wide expression profiling was conducted using whole blood-derived RNA from 98 children with septic shock, followed by a series of bioinformatic approaches targeted at subclass discovery and characterization. Results: Three putative subclasses (subclasses A, B, and C) were initially identified based on an empiric, discovery-oriented expression filter and unsupervised hierarchical clustering. Statistical comparison of the 3 putative subclasses (ANOVA, Bonferonni correction, p < 0.05) identified 6,934 differentially regulated genes. K means clustering of these 6,934 genes generated 10 coordinately regulated gene clusters corresponding to multiple signaling and metabolic pathways, all of which were differentially regulated across the 3 subclasses. Leave one out cross validation procedures indentified 100 genes having the strongest predictive values for subclass identification. Forty-four of these 100 genes corresponded to signaling pathways relevant to the adaptive immune system and glucocorticoid receptor signaling, the majority of which were repressed in subclass A patients. Subclass A patients were also characterized by repression of genes corresponding to zinc-related biology. Phenotypic analyses revealed that subclass A patients were younger, had a higher illness severity, and a higher mortality rate than patients in subclasses B and C. Conclusions: Genome-wide expression profiling can identify pediatric septic shock subclasses having clinically relevant phenotypes.
Identification of pediatric septic shock subclasses based on genome-wide expression profiling.
Age, Specimen part, Disease, Disease stage
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 SamplesIn an ongoing translational research program involving microarray-based expression profiles in pediatric septic shock, we have now conducted longitudinal studies focused on the temporal expression profiles of canonical signaling pathways and gene networks. Genome-level expression profiles were generated from whole blood-derived RNA samples of children with septic shock (n = 30 individual patients) corresponding to days 1 and 3 of admission to the pediatric intensive care unit. Based on sequential statistical and expression filters, day 1 and day 3 of septic shock were characterized by differential regulation of 2,142 and 2,504 gene probes, respectively, relative to normal control patients. Venn analysis demonstrated 239 unique genes in the day 1 data set, 598 unique genes in the day 3 data set, and 1,906 genes common to both data sets. Analyses targeted toward derivation of biological function from these data sets demonstrated time-dependent, differential regulation of genes involved in multiple canonical signaling pathways and gene networks primarily related to immunity and inflammation. Notably, multiple and distinct gene networks involving T cell- and MHC antigen-related biological processes were persistently downregulated from day 1 to day 3. Further analyses demonstrated large scale and persistent downregulation of genes corresponding to functional annotations related to zinc homeostasis. These data represent the largest reported cohort of patients with septic shock, which has undergone longitudinal genome-level expression profiling. The data further advance our genome-level understanding of pediatric septic shock and support novel hypotheses that can be readily tested at both the experimental and translational levels.
Genome-level longitudinal expression of signaling pathways and gene networks in pediatric septic shock.
No sample metadata fields
View SamplesWe sequenced mRNA from triplicate log-phase cultures of BY4741 (WT) transformed with pRS313-HA3-SSN6 and taf14D transformed with pRS313-HA3-SSN6 (empty vector), full-length pRS313-TAF14-HA3-SSN6, or pRS313-taf14W81A-HA3-SSN6 cultured in synthetic complete media lacking histidine. Overall design: Examination of changes in gene expression when the YEATS domain of Taf14 is mutated so it cannot bind acetyl-H3.
Association of Taf14 with acetylated histone H3 directs gene transcription and the DNA damage response.
Subject
View SamplesLow back pain (LBP) is one of the most prevalent conditions which need medical advice and result in chronic disabilities. Degenerative disc disease (DDD) is a common reason for LBP. A lot of researchers think that CEP degeneration play critical roles in the initiation and development of DDD. In recent years, researchers have put interests on cell-based therapies for regenerating disc structure and function. Our research team has isolated cartilage endplate-derived stem cells (CESCs) and validated their chondrogenic and osteogenic differentiation ability. Enhanced chondrogenic differentiation and inhibited osteogenic differentiation of CESCs may retard CEP calcification and restore the nutrition supply, possibly regenerating the degenerated discs.
Global Gene Expression Profiling and Alternative Splicing Events during the Chondrogenic Differentiation of Human Cartilage Endplate-Derived Stem Cells.
Specimen part
View SamplesNormal children, children with SIRS, children with sepsis, and children with septic shock.
Genomic expression profiling across the pediatric systemic inflammatory response syndrome, sepsis, and septic shock spectrum.
No sample metadata fields
View SamplesRationale: We previously generated genome-wide expression data in children with septic shock, based on whole blood-derive RNA, having the potential to lead the field into novel areas of investigation.
Validating the genomic signature of pediatric septic shock.
Sex
View SamplesGoal of the experiment: To identify correlated genes, pathways and groups of patients with systemic inflammatory response syndrome and septic shock that is indicative of biologically important processes active in these patients.
Genome-level expression profiles in pediatric septic shock indicate a role for altered zinc homeostasis in poor outcome.
No sample metadata fields
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