To more concretely elucidate the long-term effects of chronic SSRI exposure during adulthood, the long-term consequences of chronic fluoxetine (12 mg/kg) versus vehicle treatment during adulthood (postnatal day (PND) 67-88) on gene expression in the hippocampus were investigated. The study showed that adult chronic fluoxetine exposure causes on the long-term changes in the expression of genes related to, amongst others, myelination Overall design: Comparison of gene expression in hippocampus tissue of fluoxetine and methylcellulose-exposed rats (postnatal day 128). 2 rats pooled per sample, 2 samples per treatment group
Long-term consequences of chronic fluoxetine exposure on the expression of myelination-related genes in the rat hippocampus.
No sample metadata fields
View SamplesHere we characterized the transcriptome and epigenome of control keratinocytes during differentiation. Epigenomic analyses showed that the temporal enrichment of p63 motifs in dynamic enhancers underscores the key role of p63 in orchestrating the enhancer landscape during keratinocyte differentiation. The cooperation between p63 and its co-regulating factors, such as RUNX1, is important for the finetuning of gene expression. Overall design: RNA-Seq, H3K4me3 ChIP-Seq and H3K27me3 ChIP-Seq of keratinocytes during differentiation on day0(proliferation), day2(early differentiation), day4(mid differentiation) and day7(late differentiation). RUNX1 ChIP-Seq of keratinocytes at the proliferation stage(day0).
Mutant p63 Affects Epidermal Cell Identity through Rewiring the Enhancer Landscape.
No sample metadata fields
View SamplesThe ability to assign expression patterns to individual cell types that constitute a tissue is a major challenge in RNA expression analysis. This especially applies to brain given the plethora of different cells coexisting in that tissue. Here, we derived cell-type specific transcriptome signatures from existing single cell RNA data and integrated these signatures with a newly generated dataset of expression (bulk RNA-seq) of the postnatal developing hippocampus. This integrated analysis allowed us to provide a comprehensive and unbiased prediction of the differentiation drivers for 10 different hippocampal cell types and describe how the different cell types interact to support crucial developmental stages. Our integrated analysis provides a reliable resource of predicted differentiation drivers and insight into the multifaceted aspects of the cells in hippocampus during development. Overall design: 21 RNA-seq samples. For the stages E15, P1, P7, P15, and P30, there are respectively 3, 4, 3, 3, and 6 RNA-seq biological replica (total 19). One RNA-seq sample has two technical replica.
Integrated transcriptional analysis unveils the dynamics of cellular differentiation in the developing mouse hippocampus.
Specimen part, Cell line, Subject
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Multi-Institutional Prospective Validation of Prognostic mRNA Signatures in Early Stage Squamous Lung Cancer (Alliance).
Sex, Age, Specimen part, Disease
View SamplesPurpose: The primary objective of the current study was to validate biomarkers to identify the 10% to 27% of patients with stage I and 35% of patients with stage IIA squamous cell carcinoma of lung (SC) who are likely to recur following surgical resection, so that these patients may be offered enrollment in clinical trials evaluating directed ACT. A secondary objective was to identify patients with stage IIB SC who are unlikely to develop recurrences and might thereby be spared the potential significant toxicity and expense of ACT.
Multi-Institutional Prospective Validation of Prognostic mRNA Signatures in Early Stage Squamous Lung Cancer (Alliance).
Sex, Age, Specimen part, Disease
View SamplesPurpose: The primary objective of the current study was to validate biomarkers to identify the 10% to 27% of patients with stage I and 35% of patients with stage IIA squamous cell carcinoma of lung (SC) who are likely to recur following surgical resection, so that these patients may be offered enrollment in clinical trials evaluating directed ACT. A secondary objective was to identify patients with stage IIB SC who are unlikely to develop recurrences and might thereby be spared the potential significant toxicity and expense of ACT.
Multi-Institutional Prospective Validation of Prognostic mRNA Signatures in Early Stage Squamous Lung Cancer (Alliance).
Sex, Age, Specimen part, Disease
View SamplesPersistent bronchial dysplasia (BD) is associated with increased risk of developing invasive squamous cell carcinoma (SCC) of the lung. We hypothesized that differences in gene expression profiles between persistent and regressive BD would identify cellular processes that underlie progression to SCC. RNA expression arrays (Affymetrix Hu 1.0) comparing baseline biopsies from 32 bronchial sites that persisted/progressed to 31 regressive sites showed 395 differentially expressed genes (ANOVA, FDR</=0.05). Thirty-one pathways showed statistically significant evidence of altered activity between the two groups. Multiple pathways were associated with cell cycle control/proliferation, inflammation, or epithelial differentiation/cell-cell adhesion. Polo-like kinase 1 (PLK1) was associated with multiple cell cycle pathways. Cultured persistent BD cells showed increased PLK1 expression, and following treatment with PLK1 inhibitor, showed induction of apoptosis, G2/M phase arrest and decreased proliferation compared to untreated cells. These effects were not seen in normal or regressive BD cultures. Inflammatory pathway activity was decreased in persistent BD and the presence of an inflammatory infiltrate was more common in regressive BD. Regressive BDs were also associated with trends toward overall increases in macrophages and T-lymphocytes and altered polarization of these inflammatory cell subsets. Increased desmoglein 3 and plakoglobin expression was associated with higher grade and persistence of BD. The results identify alterations in cell cycle control, inflammatory activity, and epithelial differentiation/cell-cell adhesion in the persistent subset of BDs that are associated with high risk for progression to invasive SCC. These pathways may provide strong markers of risk and effective targets for lung cancer prevention.
Altered Cell-Cycle Control, Inflammation, and Adhesion in High-Risk Persistent Bronchial Dysplasia.
Age, Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Penetrance of biallelic SMARCAL1 mutations is associated with environmental and genetic disturbances of gene expression.
Sex, Specimen part
View SamplesBiallelic mutations of the DNA annealing helicase SMARCAL1 (SWI/SNF-related matrix-associated actin-dependent regulator of chromatin, subfamily a-like 1) cause Schimke immuno-osseous dysplasia (SIOD, MIM 242900), an incompletely penetrant autosomal recessive disorder. Using human, Drosophila, and mouse models, we show that the proteins encoded by SMARCAL1 orthologues localize to transcriptionally active chromatin and modulate gene expression. We also show that similar to SIOD patients, deficiency of the SMARCAL1 orthologues alone is insufficient to cause disease in fruit flies and mice although such deficiency causes modest diffuse alterations in gene expression. Rather, disease manifests when SMARCAL1 deficiency interacts with genetic and environmental factors that further alter gene expression. We conclude that the SMARCAL1 annealing helicase buffers fluctuations in gene expression and that alterations in gene expression contribute to the penetrance of SIOD.
Penetrance of biallelic SMARCAL1 mutations is associated with environmental and genetic disturbances of gene expression.
Sex, Specimen part
View SamplesBiallelic mutations of the DNA annealing helicase SMARCAL1 (SWI/SNF-related matrix-associated actin-dependent regulator of chromatin, subfamily a-like 1) cause Schimke immuno-osseous dysplasia (SIOD, MIM 242900), an incompletely penetrant autosomal recessive disorder. Using human, Drosophila, and mouse models, we show that the proteins encoded by SMARCAL1 orthologues localize to transcriptionally active chromatin and modulate gene expression. We also show that similar to SIOD patients, deficiency of the SMARCAL1 orthologues alone is insufficient to cause disease in fruit flies and mice although such deficiency causes modest diffuse alterations in gene expression. Rather, disease manifests when SMARCAL1 deficiency interacts with genetic and environmental factors that further alter gene expression. We conclude that the SMARCAL1 annealing helicase buffers fluctuations in gene expression and that alterations in gene expression contribute to the penetrance of SIOD. Overall design: The RNA sequencing libraries were constructed from the liver RNA of 3-4-month Smarcal1del/del and wt female mice (n=3/group) at 20°C and after 1 hour at 39.5°C. These libraries were sequenced using the whole transcriptome shotgun sequencing procedure.
Penetrance of biallelic SMARCAL1 mutations is associated with environmental and genetic disturbances of gene expression.
Sex, Specimen part, Cell line, Subject
View Samples