Analysis of differential gene expression in C. elegans adults exposed to three different bacteria: E. coli strain OP50, wild-type P. aeruginosa PA14 and gacA mutant PA14. Samples were analyzed at 4 hours and 8 hours after exposure to the different bacteria. These studies identified C. elegans genes induced by pathogen infection.
p38 MAPK regulates expression of immune response genes and contributes to longevity in C. elegans.
Specimen part
View SamplesAnalysis of genes differentially expressed between daf-2(e1368) and daf-2(e1368);pmk-1(km25) and between daf-2(e1368) and daf-2(e1368);daf-16(mgDf47). These studies identified genes upregulated by wild-type PMK-1 and wild-type DAF-16.
p38 MAPK regulates expression of immune response genes and contributes to longevity in C. elegans.
Specimen part
View SamplesObstructive sleep apnea (OSA) leads to increased cardiovascular morbidity and mortality, which have been attributed to intermittent hypoxia (IH). The effects of IH on lung structure and function are unknown. We used a mouse model of chronic IH, which mimics the O2 profile in patients with OSA. We exposed adult C57BL/6J mice to 3 months of IH with an FIO2 nadir of 5%, 60 times/hr during the 12hr light phase. Control mice were exposed to room air.
Chronic intermittent hypoxia induces lung growth in adult mice.
Sex, Specimen part
View SamplesIntegration of multi-omics data remains a key challenge in fulfilling the potential of comprehensive systems biology.
OnPLS-Based Multi-Block Data Integration: A Multivariate Approach to Interrogating Biological Interactions in Asthma.
Sex, Age, Specimen part, Disease, Disease stage
View SamplesTumor metastasis remains the major cause of cancer-related death, but its molecular basis is still not well understood. Here we uncovered a splicing-mediated pathway that is essential for breast cancer metastasis. We show that the RNA-binding protein hnRNPM promotes breast cancer metastasis by activating the switch of alternative splicing that occurs during epithelial-mesenchymal transition (EMT). Genome-wide deep sequencing analysis suggests that hnRNPM potentiates TGFb signaling and identifies CD44 as a key downstream target of hnRNPM. hnRNPM ablation prevents TGFb-induced EMT and inhibits breast cancer metastasis in mice, whereas enforced expression of the specific CD44s splice isoform overrides the loss of hnRNPM and permits EMT and metastasis. Mechanistically, we demonstrate that the ubiquitously expressed hnRNPM acts in a mesenchymal-specific manner to precisely control CD44 splice isoform switching during EMT. This restricted cell-type activity of hnRNPM is achieved by competition with ESRP1, an epithelial-splicing regulator that binds to the same cis-regulatory RNA elements and is repressed during EMT. Importantly, hnRNPM is associated with aggressive breast cancer and correlates with increased CD44s in patient specimens. These findings demonstrate a novel molecular mechanism through which tumor metastasis is endowed by the hnRNPM-mediated splicing program. Overall design: RNAseq for control, hnRNPM siRNA treated lung metastatic LM2 clonal line, derived from the mesenchymal MDA-MB-231 cells
Cell type-restricted activity of hnRNPM promotes breast cancer metastasis via regulating alternative splicing.
No sample metadata fields
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Evidence for compensatory upregulation of expressed X-linked genes in mammals, Caenorhabditis elegans and Drosophila melanogaster.
Sex, Specimen part, Cell line, Treatment
View SamplesExpression levels of human genes vary extensive among individuals. Gene expression determines cell function and characteristics thus this variation likely contributes to phenotypic variation. Genetic studies have shown that there is a heritable component to gene expression variation, and have identified genomic regions that contain polymorphic regulators. However, most of these regions are quite large, and few regulators have been identified. In this genetic of gene expression study, we used a large sample to search the genome for polymorphic regulators that influence gene expression, and followed up the results with deep sequencing of transcriptomes and molecular analyses. Key word(s): Transcriptome Analysis Overall design: genetics of gene expression study, 41 Coriell cell line samples examined.
Evidence for compensatory upregulation of expressed X-linked genes in mammals, Caenorhabditis elegans and Drosophila melanogaster.
No sample metadata fields
View SamplesBoth transcription and post-transcriptional processes, such as alternative splicing, play crucial roles in controlling developmental programs in metazoans. Recently emerged RNA-seq method has brought our understanding of eukaryotic transcriptomes to a new level, because it can resolve both gene expression level and alternative splicing events simultaneously. To gain a better understanding of cellular differentiation in gonads, we analyzed mRNA profiles from Drosophila testes and ovaries using RNA-seq. We identified a set of genes that have sex-specific isoforms in wild-type (WT) gonads, including several transcription factors. We found that differentiation of sperms from undifferentiated germ cells induced a dramatic downregulation of RNA splicing factors. Our data confirmed that RNA splicing events are significantly more frequent in the undifferentiated cell-enriched bag of marbles (bam) mutant testis, but downregulated upon differentiation in WT testis. Consistent with this, we showed that genes required for meiosis and terminal differentiation in WT testis were mainly regulated at the transcriptional level, but not by alternative splicing. Unexpectedly, we observed an increase in expression of all families of chromatin remodeling factors and histone modifying enzymes in the undifferentiated cell-enriched bam testis. More interestingly, chromatin regulators and histone modifying enzymes with opposite enzymatic activities are coenriched in undifferentiated cells in testis, suggesting that these cells may possess dynamic chromatin architecture. Finally, our data revealed many new features of the Drosophila gonadal transcriptomes, and will lead to a more comprehensive understanding of how differential gene expression and splicing regulate gametogenesis in Drosophila. Our data provided a foundation for the systematic study of gene expression and alternative splicing in many interesting areas of germ cell biology in Drosophila, such as the molecular basis for sexual dimorphism and the regulation of the proliferation vs terminal differentiation programs in germline stem cell lineages. Overall design: RNA-Seq experiments for four Drosophila melanogaster samples: (1) bam mutant testes, (2) wild-type testes, (3) bam mutant ovaries, (4) wild-type ovaries
Evidence for compensatory upregulation of expressed X-linked genes in mammals, Caenorhabditis elegans and Drosophila melanogaster.
Specimen part, Subject
View SamplesOne of the most common genetic alterations in acute myeloid leukemia is the internal tandem duplication (ITD) in the FLT3 receptor for cytokine FLT3 ligand (FLT3L). The constitutively active FLT3-ITD promotes the expansion of transformed progenitors, but also has pleiotropic effects on normal hematopoiesis. We analyzed the effect of FLT3-ITD on dendritic cells (DCs), which express FLT3 and can be expanded by FLT3L administration. We report that young pre-leukemic mice with the Flt3ITD knock-in allele manifest an expansion of all DCs including classical (cDCs) and plasmacytoid (pDCs). The expansion originated in DC progenitors, occurred in a cell-intrinsic manner and was further enhanced in Flt3ITD/ITD mice. The mutation caused the downregulation of Flt3 on the surface of DCs and reduced their responsiveness to Flt3L. Flt3ITD mice showed enhanced capacity to support T cell proliferation, including a cell-extrinsic expansion of regulatory T cells (Tregs). Accordingly, these mice restricted alloreactive T cell responses during graft-versus-host reaction, but failed to control autoimmunity in the absence of Tregs. Thus, the FLT3-ITD mutation directly affects DC development, thereby indirectly modulating T cell homeostasis and supporting Treg expansion. This effect of FLT3-ITD may subvert immunosurveillance and promote leukemogenesis in a cell-extrinsic manner. Overall design: Sorted splenic dendritic cell subsets from either Flt3+/+ or Flt3ITD/+ mice were sequenced for mRNA profiling. For each subset per genotype contains 2-3 replicates, all from independent experiments.
Leukemia-associated activating mutation of Flt3 expands dendritic cells and alters T cell responses.
Specimen part, Cell line, Subject
View SamplesImmunoadsorption with subsequent immunoglobulin substitution (IA/IgG) represents a therapeutic approach for patients with dilated cardiomyopathy (DCM). Here, we studied which molecular cardiac alterations are initiated after this treatment.
Changes of myocardial gene expression and protein composition in patients with dilated cardiomyopathy after immunoadsorption with subsequent immunoglobulin substitution.
Sex, Age, Disease
View Samples