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GSE21795
Homo sapiens
6 Downloadable Samples
Affymetrix Human Exon 1.0 ST Array [probe set (exon) version (huex10st)
Description
Myotonic dystrophes (DM), the most common adult muscular dystrophy, are the first recognized examples of RNA-mediated diseases in which expression of mutant RNAs containing expanded CUG or CCUG repeats interfere with the splicing of other mRNAs. Using whole-genome microarrays, we found that alternative splicing of the BIN1 mRNA is altered in DM skeletal muscle tissues, resulting in the expression of an inactive form of BIN1 deprived of phosphoinositide-binding and membrane-tubulating activities. BIN1 is involved in tubular invaginations of the plasma membrane and is essential for biogenesis of the muscle T-tubules, which are specialized skeletal muscle membrane structures essential to correct excitation-contraction (E-C) coupling. Mutations in the BIN1 gene cause centronuclear myopathy (CNM) that shares some histopathological features with DM, and both diseases are characterized by muscle weakness. Consistent with a loss-of-function of BIN1, muscle T-tubules were altered in DM patients, and membrane tubulation was restored upon expression of the correct splicing form of BIN1 in DM muscle cells. By deciphering the mechanism of BIN1 splicing mis-regulation we demonstrate that the splicing regulator, MBNL1, which is sequestered by expanded CUG and CCUG in DM, binds the BIN1 pre-mRNA and regulates directly its alternative splicing. Finally, reproducing BIN1 splicing alteration in mice is sufficient to reproduce the DM features of T-tubule alterations and muscle weakness. We propose that alteration of BIN1 alternative splicing regulation leads to muscle weakness, a predominant pathological feature of DM.
Publication Title
Misregulated alternative splicing of BIN1 is associated with T tubule alterations and muscle weakness in myotonic dystrophy.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 384 Downloadable Samples
Illumina HiSeq 4000
Description
Non-typhoidal Salmonella (NTS) are among of the most important food-borne pathogens. Recently, a highly invasive multi-drug resistant S. Typhimurium of a distinct multilocus sequence type (MLST), ST313, has emerged across sub-Saharan Africa as a major cause of lethal bacteraemia in children and immunosuppressed adults. Encounters between dendritic cells (DCs) and invading bacteria determine the course of infection but whether or how ST313 might usurp DC mediated defence has not been reported. Here we utilised fluorescently labelled invasive and non-invasive strains of Salmonella combined with single-cell RNA sequencing to study the transcriptomes of individual infected and bystander DCs. The transcriptomes displayed a repertoire of cell instrinsic and extrinsic innate response states that differed between invasive and non-invasive strains. Gene expression heterogeneity was increased in DCs challenged with invasive Salmonella. DCs exposed but not harbouring invasive Salmonella exhibited a hyper-activated profile that likely facilitates trafficking of infected cells and dissemination of internalised intact bacteria. In contrast, invasive Salmonella containing DCs demonstrate reprogramming of trafficking genes required to avoid autophagic destruction. Furthermore, these cells displayed differential expression of tolerogenic IL10 and MARCH1 enabling CD83 mediated adaptive immune evasion. Altogether our data illustrate pathogen cell-to cell variability directed by a Salmonella invasive strain highlighting potential mechanisms of host adaption with implications for dissemination in vivo. Overall design: Single-cell RNA sequencing (SMARTSeq2) of 373 human monocyte derived dendritic cells infected with S. Typhimurium strain LT2 or D23580 or left uninfected
Publication Title
Invasive Salmonella exploits divergent immune evasion strategies in infected and bystander dendritic cell subsets.
Sample Metadata Fields
Subject, Time
View Samples- Homo sapiens
- 45 Downloadable Samples
- Illumina HiSeq 4000
Description
Non-typhoidal Salmonella (NTS) are among of the most important food-borne pathogens. Recently, a highly invasive multi-drug resistant S. Typhimurium of a distinct multilocus sequence type (MLST), ST313, has emerged across sub-Saharan Africa as a major cause of lethal bacteraemia in children and immunosuppressed adults. Encounters between dendritic cells (DCs) and invading bacteria determine the course of infection but whether or how ST313 might usurp DC mediated defence has not been reported. Here we utilised fluorescently labelled invasive and non-invasive strains of Salmonella combined with single-cell RNA sequencing to study the transcriptomes of individual infected and bystander DCs. The transcriptomes displayed a repertoire of cell instrinsic and extrinsic innate response states that differed between invasive and non-invasive strains. Gene expression heterogeneity was increased in DCs challenged with invasive Salmonella. DCs exposed but not harbouring invasive Salmonella exhibited a hyper-activated profile that likely facilitates trafficking of infected cells and dissemination of internalised intact bacteria. In contrast, invasive Salmonella containing DCs demonstrate reprogramming of trafficking genes required to avoid autophagic destruction. Furthermore, these cells displayed differential expression of tolerogenic IL10 and MARCH1 enabling CD83 mediated adaptive immune evasion. Altogether our data illustrate pathogen cell-to cell variability directed by a Salmonella invasive strain highlighting potential mechanisms of host adaption with implications for dissemination in vivo. Overall design: RNA-seq of mini-bulks (5000 cells) of human monocyte derived dendritic cells infected with S. Typhimurium strain LT2 or D23580 or left uninfected
Publication Title
Invasive Salmonella exploits divergent immune evasion strategies in infected and bystander dendritic cell subsets.
Sample Metadata Fields
Subject, Time
View Samples- Mus musculus
- 9 Downloadable Samples
- Affymetrix Mouse Expression 430A Array (moe430a)
Description
To understand the developing striatum, key genes during development were identified using microarray analsyis tha could be considered as marker of medium spiny neurons. The ages studied is at peak striatal neurogenesis.
Publication Title
FoxP1 marks medium spiny neurons from precursors to maturity and is required for their differentiation.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 33 Downloadable Samples
- Illumina HiSeq 2500
Description
The goal of this study was to define relationships between peripheral blood miRNAs and mRNAs of women undergoing idiopathic preterm labor (PTL) and compare network level changes to control women that deliver at term.Using RNA Sequencing we have performed global miRNA and mRNA profiling in both monocytes and whole blood leukocytes of women who underwent PTL (N=15) matched to non-pathological controls (N=30) as a part of the Ontario Birth Study cohort. We have identified differentially expressed miRNAs, mRNAs and pathways associated with PTL. Intriguingly, we found perturbations in many cellular signaling pathways, particularly in interleukin signaling. We also predicted mRNA targets for specific miRNAs and used these predictions to build putative miRNA-mRNA networks. We identified 6 miRNAs significantly associated with PTL whose expression is negatively correlated with expression of 14 predicted mRNA targets that are also significantly associated with PTL. Overall design: miRNA and mRNA were quantified from whole blood and monocytes of women undergoing spontaneous preterm labor compared to nonlabor controls matched on gestational age
Publication Title
Comparative analysis of gene expression in maternal peripheral blood and monocytes during spontaneous preterm labor.
Sample Metadata Fields
Subject
View Samples- Homo sapiens
- 24 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
In this study we analyzed the behavior of bone marrow MSC (BM-MSC) from MPN patients with the mutation in JAK2V617F. We initially characterized the biological function and gene expression profile changes in BM-MSC from MPN patients when compared to BM-MSC of healthy donors (HD). Then, we established co-cultures between MSC cell lines (HTERT and HS5) and the UKE-1 MPN cell line, and performed RT-PCR to study if the leukemic cells were able to modify the genes related to hematopoietic support.
Publication Title
Mesenchymal stromal cells (MSC) from JAK2+ myeloproliferative neoplasms differ from normal MSC and contribute to the maintenance of neoplastic hematopoiesis.
Sample Metadata Fields
Specimen part, Disease stage, Subject
View Samples- Mus musculus, Homo sapiens, Rattus norvegicus
- 15 Downloadable Samples
Illumina ratRef-12 v1.0 expression beadchip
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Molecular Liver Cancer Prevention in Cirrhosis by Organ Transcriptome Analysis and Lysophosphatidic Acid Pathway Inhibition.
Sample Metadata Fields
Sex, Specimen part, Disease, Treatment
View Samples- Mus musculus
- 15 Downloadable Samples
- Illumina ratRef-12 v1.0 expression beadchip
Description
Gene-expression profiles of liver tissue of cabon tetrachloride (CCl4)-treated and control mice were obtained before and after organotypic ex vivo tissue culture.
Publication Title
Molecular Liver Cancer Prevention in Cirrhosis by Organ Transcriptome Analysis and Lysophosphatidic Acid Pathway Inhibition.
Sample Metadata Fields
Specimen part
View Samples- Rattus norvegicus
- 18 Downloadable Samples
- Illumina ratRef-12 v1.0 expression beadchip
Description
CHD5 is frequently deleted in neuroblastoma, and appears to be a tumor suppressor gene; however, little is known about the role of CHD5. We found CHD5 mRNA was restricted to brain; by contrast most other remodeling ATPases were broadly expressed. CHD5 protein isolated from mouse brain was associated with HDAC2, p66, MTA3 and RbAp46 in a megadalton complex. CHD5 protein was detected in several rat brain regions and appeared to be enriched in neurons. CHD5 protein was predominantly nuclear in primary rat neurons and brain sections. Microarray analysis revealed genes that were upregulated and downregulated when CHD5 was depleted from primary neurons. CHD5 depletion altered expression of neuronal genes, transcription factors, and brain-specific subunits of the SWI/SNF remodeling enzyme. Aging and Alzheimers gene sets were strongly affected by CHD5 depletion from primary neurons. Chromatin immunoprecipitation revealed CHD5 bound to these genes, suggesting the regulation was direct. Together, these results indicate that CHD5 is found in a NuRD-like multi-protein complex. CHD5 is restricted to the brain, unlike the closely related family members CHD3 and CHD4. CHD5 regulates expression of neuronal genes, cell cycle genes and remodeling genes. CHD5 is linked to regulation of aging and Alzheimers genes.
Publication Title
CHD5, a brain-specific paralog of Mi2 chromatin remodeling enzymes, regulates expression of neuronal genes.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 12 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
Cancer progression is associated with alterations of epigenetic regulators such as histone-lysine demethylases 4 (KDM4)2-5. During breast cancer therapy, classical treatments fail to address resistant cancer stem cell populations6-10. Here, we identified a novel KDM4 inhibitor (KDM4(i)) with unique preclinical characteristics. KDM4(i) is a highly potent pan KDM4 inhibitor that specifically blocks the demethylase activity of KDM4A, B, C, and D but not that of the other members of the KDM family. We validated the KDM4(i) anti-tumoral properties under conditions recapitulating patient tumors. Therefore, we established a method to isolate and grow triple-negative breast cancer stem cells (BCSCs) from individual patient tumors after neoadjuvant chemotherapy. Limiting dilution orthotopic xenografts of these BCSCs faithfully regenerate original patient tumor histology and gene expression. KDM4(i) blocks proliferation, sphere formation and xenograft tumor growth of BCSCs. Importantly, KDM4(i) abrogates expression of EGFR, a driver of therapy-resistant triple-negative breast tumor cells11, via inhibition of the KDM4A demethylase activity. Taken together, we present a unique BCSC culture system as a basis for therapeutic compound identification and demonstrate that KDM4 inhibition is a new therapeutic strategy for the treatment of triple-negative breast cancer.
Publication Title
KDM4 Inhibition Targets Breast Cancer Stem-like Cells.
Sample Metadata Fields
Sex, Specimen part, Subject
View Samples