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SRP188078
Drosophila melanogaster
66 Downloadable Samples
Illumina HiSeq 2000
Description
The 1.6 Mbp deletion on chromosome 3q29 is associated with a range of neurodevelopmental disorders, including schizophrenia, autism, microcephaly, and intellectual disability. Despite its importance towards neurodevelopment, the role of individual genes, genetic interactions, and disrupted biological mechanisms underlying the deletion have not been thoroughly characterized. Here, we used quantitative methods to assay Drosophila melanogaster and Xenopus laevis models with tissue-specific individual and pairwise knockdown of 14 homologs of genes within the 3q29 region. We identified developmental, cellular, and neuronal phenotypes for multiple homologs of 3q29 genes, potentially due to altered apoptosis and cell cycle mechanisms during development. Using the fly eye, we screened for 314 pairwise knockdowns of homologs of 3q29 genes and identified 44 interactions between pairs of homologs and 34 interactions with other neurodevelopmental genes. Interestingly, NCBP2 homologs in Drosophila (Cbp20) and X. laevis (ncbp2) enhanced the phenotypes of homologs of the other 3q29 genes, leading to significant increases in apoptosis that disrupted cellular organization and brain morphology. These cellular and neuronal defects were rescued with overexpression of the apoptosis inhibitors Diap1 and xiap in both models, suggesting that apoptosis is one of several potential biological mechanisms disrupted by the deletion. NCBP2 was also highly connected to other 3q29 genes in a human brain-specific interaction network, providing support for the relevance of our results towards the human deletion. Overall, our study suggests that NCBP2-mediated genetic interactions within the 3q29 region disrupt apoptosis and cell cycle mechanisms during development. Overall design: mRNA-sequencing of Drosophila neuron-specific RNAi knockdown (whole head) for four individual 3q29 homologs (DLG1, NCBP2, FBXO45, and PAK2), two pairwise knockdowns of 3q29 homologs (NCBP2/DLG1 and NCBP2/FBXO45), and two VDRC wild-type controls (GD and KK backgrounds). Sequencing was performed using Illumina HiSeq 2000 on three biological replicates per sample, with two-three technical replicates per biological replicate.
Publication Title
NCBP2 modulates neurodevelopmental defects of the 3q29 deletion in Drosophila and Xenopus laevis models.
Sample Metadata Fields
Specimen part, Subject
View Samples- Mus musculus
- 12 Downloadable Samples
Affymetrix Mouse Gene 2.0 ST Array (mogene20st)
Description
Objective: Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system (CNS), characterized by a global increasing incidence driven by relapsing-remitting disease in females. p38 MAP kinase (MAPK) has been described as a key regulator of inflammatory responses in autoimmunity, but its role in the sexual dimorphism in MS or MS models remains unexplored. Methods: Toward this end, we used experimental autoimmune encephalomyelitis (EAE), the principal animal model of MS, combined with pharmacologic and genetic inhibition of p38 MAPK activity and transcriptomic analyses. Results: Pharmacologic inhibition of p38 MAPK selectively ameliorated EAE in female mice. Conditional deletion studies demonstrated that p38 signaling in macrophages/myeloid cells, but not T cells or dendritic cells, recapitulated this sexual dimorphism. Analysis of CNS inflammatory infiltrates showed that female, but not male mice lacking p38 in myeloid cells exhibited reduced immune cell activation compared with controls, while peripheral T cell priming was unaffected in both sexes. Transcriptomic analyses of myeloid cells revealed differences in p38-controlled transcripts comprising female- and male-specific gene modules, with greater p38 dependence of pro-inflammatory gene expression in females. Interpretation: Our findings demonstrate a key role for p38 in myeloid cells in CNS autoimmunity and uncover important molecular mechanisms underlying sex differences in disease pathogenesis. Taken together, our results suggest that the p38 MAPK signaling pathway represents a novel target for much needed disease modifying therapies for MS
Publication Title
Sex-specific control of central nervous system autoimmunity by p38 mitogen-activated protein kinase signaling in myeloid cells.
Sample Metadata Fields
Sex, Specimen part
View Samples- Mus musculus
- 6 Downloadable Samples
- Illumina MouseWG-6 v2.0 expression beadchip
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Genome-wide targeting of the epigenetic regulatory protein CTCF to gene promoters by the transcription factor TFII-I.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Mus musculus
- 6 Downloadable Samples
- Illumina MouseWG-6 v2.0 expression beadchip
Description
Analysis of the effect of TFII-I depletion on gene expression Wehi-231 cell lines.
Publication Title
Genome-wide targeting of the epigenetic regulatory protein CTCF to gene promoters by the transcription factor TFII-I.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Genome 430A 2.0 Array (mouse430a2)
Description
IL-6, a proinflammtory cytokine produced by antigen presenting cells and non-hematopoietic cells in response to external stimuli, acts as an important bridge between the innate and adaptive immune responses. IL-6 together with IL-4 can promote Th2 polarization, while in combination with TGFbeta mediates Th17 differentiation. We examined early changes in gene expression in mouse CD4+ T cells induced by IL-6.
Publication Title
The induction of antibody production by IL-6 is indirectly mediated by IL-21 produced by CD4+ T cells.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 14 Downloadable Samples
- NextSeq 500
Description
We report gene expression data for the human cell lines HL-60 and PLB-985, which serve as models for human neutrophils. We measured gene expression using RNA-Seq for these cell lines both prior and after differentiation into a neutrophil-like state using two differentiation protocols (treatment with DMSO or treatment with DMSO and replacement of serum with Nutridoma). Overall design: HL-60 and PLB-985 cells grown in culture were processed for RNA-Seq both before and after differentiation for six days in media supplemented with 1.3% dimethyl sulfoxide (DMSO). The cell lines were also analyzed after differentiation for six days in media with 1.3% DMSO, reduced serum (0.5% FBS), and Nutridoma-CS (2%). PLB-985 cells were also analyzed at intermediate time points of 2 days and 4 days with the Nutridoma protocol.
Publication Title
A map of gene expression in neutrophil-like cell lines.
Sample Metadata Fields
Cell line, Subject
View Samples- Homo sapiens
- 29 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Mononuclear phagocytes (MPs), including monocytes and macrophages, play complex roles in the pathogenesis of age-related macular degeneration (AMD). We aimed to perform global transcriptome analysis on monocytes from AMD patients to obtain additional insight to the role of MPs in AMD. Peripheral blood was taken from treatment-nave neovascular AMD (nvAMD) patients (n=14), and age-matched controls (n=15). Peripheral blood mononuclear cells (PBMCs) were separated and monocytes were isolated via negative selection. Gene expression was evaluated with Affymetrix Gene1.0 ST microarrays. Statistical/bioinformatics analysis was performed using open sourceware programs.
Publication Title
Transcriptome Analysis on Monocytes from Patients with Neovascular Age-Related Macular Degeneration.
Sample Metadata Fields
Specimen part, Disease, Disease stage
View Samples- Rattus norvegicus
- 24 Downloadable Samples
- Affymetrix Rat Genome 230 2.0 Array (rat2302)
Description
We show that infant trauma, as modeled by infant paired odor-shock conditioning, results in later life depressive-like behavior that can be modulated by learned infant cues (i.e., odor previously paired with shock). We have previously shown that this infant attachment odor learning paradigm results in the creation of a new artificial maternal odor that is able to control pup behavior and retain its value throughout development. Here, we assess the mechanism by which this artificial maternal odor is able to rescue depressive-like behavior and show that this anti-depressant like effect results in glucocorticoid and serotonin (5-HT) related changes in amygdala gene expression and is dependent on amygdala 5-HT. Furthermore, increasing amygdala 5-HT and blocking corticosterone (CORT) in the absence of odor mimics the adult rescue effects elicited by the artificial maternal odor, suggesting a mechanism by which odor presentation exerts its repair effects.
Publication Title
Enduring good memories of infant trauma: rescue of adult neurobehavioral deficits via amygdala serotonin and corticosterone interaction.
Sample Metadata Fields
Specimen part
View Samples- Rattus norvegicus
- 18 Downloadable Samples
- Affymetrix Rat Gene 1.0 ST Array (ragene10st)
Description
Cyclosporin A induces expression of proapoptotic factors when cells are challenged by increased tonicity
Publication Title
Cyclosporin-A induced toxicity in rat renal collecting duct cells: interference with enhanced hypertonicity induced apoptosis.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Mus musculus, Rattus norvegicus
- 11 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
A series contains a set of transcript intensity values measured by Affymetrix microarray.
Publication Title
Systems-level analysis of cell-specific AQP2 gene expression in renal collecting duct.
Sample Metadata Fields
Sex, Specimen part
View Samples