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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- Drosophila melanogaster
- 63 Downloadable Samples
- Illumina HiSeq 2000
Description
As opposed to syndromic CNVs caused by single genes, extensive phenotypic heterogeneity in variably-expressive CNVs complicates disease gene discovery and functional evaluation. Here, we propose a complex interaction model for pathogenicity of the autism-associated 16p11.2 deletion, where CNV genes interact with each other in conserved pathways to modulate expression of the phenotype. Using multiple quantitative methods in Drosophila RNAi lines, we identify a range of neurodevelopmental phenotypes for knockdown of individual 16p11.2 homologs in different tissues. We test 565 pairwise knockdowns in the developing eye, and identify 24 interactions between pairs of 16p11.2 homologs and 46 interactions between 16p11.2 homologs and neurodevelopmental genes that suppress or enhance cell proliferation phenotypes compared to one-hit knockdowns. These interactions within cell proliferation pathways are also enriched in a human brain-specific network, providing translational relevance in humans. Our study indicates a role for pervasive genetic interactions within CNVs towards cellular and developmental phenotypes. Overall design: mRNA-sequencing of Drosophila neuron-specific knockdown model heads for six 16p11.2 homologs and wild-type control. Sequencing was performed using Illumina HiSeq 2000 on three biological replicates per sample, with three technical replicates per biological replicate.
Publication Title
Pervasive genetic interactions modulate neurodevelopmental defects of the autism-associated 16p11.2 deletion in Drosophila melanogaster.
Sample Metadata Fields
Sex, Specimen part, Subject
View Samples- Mus musculus
- 19 Downloadable Samples
Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Distinct metabolic states govern skeletal muscle stem cell fates during prenatal and postnatal myogenesis.
Sample Metadata Fields
Age, Specimen part
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Transcriptomic analysis of FACS-sorted Pax7nGFP quiescent skeletal muscle satellite cells cells from young, and old mice. Results provide knowledge about the molecular mechanisms underlying age-related skeletal muscle satellite cells homeostasis.
Publication Title
Distinct metabolic states govern skeletal muscle stem cell fates during prenatal and postnatal myogenesis.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 7 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Transcriptomic analysis of FACS-sorted Pax7nGFP quiescent skeletal muscle satellite cells cells from old, and post-mortem mice. Results provide knowledge about the molecular mechanisms underlying age-related skeletal muscle satellite cells homeostasis.
Publication Title
Distinct metabolic states govern skeletal muscle stem cell fates during prenatal and postnatal myogenesis.
Sample Metadata Fields
Age, Specimen part
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
DAZAP1 regulates the splicing of Crem, Crisp2 and Pot1a transcripts.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Deleted in Azoospermia Associated Protein 1 (DAZAP1) is a ubiquitous RNA-binding protein that is highly expressed in the testis. It is a component of the hnRNP particles and shuttles between the nucleus and the cytoplasm. Mice expressing the DAZAP1-Fn mutant protein manifest both growth retardation and spermatogenic arrest before meiosis I. To elucidate the biological function(s) of DAZAP1 and to search for its natural RNA substrates, we compared the expression profiles of wild-type and Dazap1 mutant testes by cDNA microarrays.
Publication Title
DAZAP1 regulates the splicing of Crem, Crisp2 and Pot1a transcripts.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 20 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
Resistance of Calu3 NSCLC cells to the cytotoxic nucleoside analog gemcitabine (2',2'-difluorodeoxycytidine) can be prevented as well as reversed by the rexinoid X receptor selective agonist bexarotene. This study was designed to investigate the changes in gene expression associated with gemcitabine resistance and its reversal by bexarotene. In addition to the parental Calu3 cells and the 10 cycles of treatment of the gemcitabine resistant Calu3 cells with vehicle or bexarotene, analogous treatment paradigms with gemcitabine alone as well as the combination of both compounds have been included as controls. (However, it has to be noted that in the combination treatment, cells that were re-sensitized by bexarotene have largely been removed from the culture before harvest due to the cytotoxic activity of gemcitabine.)
Publication Title
Bexarotene (LGD1069, Targretin), a selective retinoid X receptor agonist, prevents and reverses gemcitabine resistance in NSCLC cells by modulating gene amplification.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 4 Downloadable Samples
- Illumina HumanRef-8 v3.0 expression beadchip
Description
Biological effects of overexpression of miR-146b microRNAs in the A549 human lung cancer cell-line was studied. A549 cells were engineered to express the precursor RNA (pre-miR-146b) that generates the miR-146b microRNAs. Control cells were engineered using the same gene expression plasmid (pLemiR, Open Biosystems) but without the pre-miR-146b insert. The Trans-Lentiviral GIPZ packaging system (Open Biosystems) was used to generate stable transfectant populations of the engineered cells.
Publication Title
Overexpression of the lung cancer-prognostic miR-146b microRNAs has a minimal and negative effect on the malignant phenotype of A549 lung cancer cells.
Sample Metadata Fields
Disease, Cell line
View Samples- Homo sapiens
- 30 Downloadable Samples
- IlluminaGenomeAnalyzerII
Description
We used RNA-seq to interrogate prostate cancer specific gene fusions, alternative splicings, somatic mutations and novel transcripts. Overall design: We sequenced the transcriptome (polyA+) of 20 prostate cancer tumors and 10 matched normal tissues using Illumina GAII platform. Then we used bioinformatic approaches to identify prostate cancer specific aberrations which include gene fusion, alternative splicing, somatic mutation, etc.
Publication Title
Recurrent chimeric RNAs enriched in human prostate cancer identified by deep sequencing.
Sample Metadata Fields
No sample metadata fields
View Samples