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SRP090281
Mus musculus
6 Downloadable Samples
Illumina HiSeq 2500
Description
Numerous genetic variants associated with MEF2C are linked to autism, intellectual disability (ID) and schizophrenia (SCZ) – a heterogeneous collection of neurodevelopmental disorders with unclear pathophysiology. MEF2C is highly expressed in developing cortical excitatory neurons, but its role in their development remains unclear. We show here that conditional embryonic deletion of Mef2c in cortical and hippocampal excitatory neurons (Emx1-lineage) produces a dramatic reduction in cortical network activity in vivo, due in part to a dramatic increase in inhibitory and a decrease in excitatory synaptic transmission. In addition, we find that MEF2C regulates E/I synapse density predominantly as a cell-autonomous, transcriptional repressor. Analysis of differential gene expression in Mef2c mutant cortex identified a significant overlap with numerous synapse- and autism-linked genes, and the Mef2c mutant mice displayed numerous behaviors reminiscent of autism, ID and SCZ, suggesting that perturbing MEF2C function in neocortex can produce autistic- and ID-like behaviors in mice. Overall design: We carried out RNA-sequencing (RNA-seq) of somatosensory cortical tissue from control (Mef2cfl/fl) or Mef2c cKO (Mef2cfl/fl; Emx1-Cre) adult male mice. For the RNA-seq, three indipendent replicates were used for the mouse tissues.
Publication Title
MEF2C regulates cortical inhibitory and excitatory synapses and behaviors relevant to neurodevelopmental disorders.
Sample Metadata Fields
Sex, Age, Specimen part, Cell line, Subject
View Samples- Homo sapiens
- 8 Downloadable Samples
- IlluminaHiSeq2000
Description
Mutations in the gene encoding the transcription factor forkhead box P1 or FOXP1 occur in patients with neurodevelopmental disorders, including autism. However, the function of FOXP1 in the brain remains mostly unknown. Here, we identify the gene expression program regulated by FoxP1 in both human neural cells and mouse brain and demonstrate a conserved role for FOXP1 transcriptional regulation of autism and Fragile X Mental Retardation Protein (FMRP) mediated pathways. Coexpression networks support a role for Foxp1 in neuronal activity, and we show that Foxp1 is necessary for neuronal excitability. Using a Foxp1 mouse model, we observe defects in ultrasonic vocalizations. This behavioral phenotype is reflected at the genomic level as striatal Foxp1-regulated overlap with genes known to be important in rodent vocalizations. These data support an integral role for FOXP1 in regulating signaling pathways vulnerable in developmental disorders and the specific regulation of pathways important for vocal communication. Overall design: We carried out RNA-sequencing (RNA-seq) and ChIP-sequencing of human neural progenitors cells. We carried out RNA-sequencing (RNA-seq) of mouse striatal tissue, mouse hippocampal tissue and mouse cortical tissue. For the RNA-seq, four indipendent replicates were used for the neural progenitor cells and mouse tissues. For the Chip-seq, a single neural progenitor cell line was used.
Publication Title
FoxP1 orchestration of ASD-relevant signaling pathways in the striatum.
Sample Metadata Fields
No sample metadata fields
View Samples- Drosophila melanogaster
- 23 Downloadable Samples
Affymetrix Drosophila Genome Array (drosgenome1)
Description
A study evaluating the effect of stress resistance selection of Drosophila melanogaster.
Publication Title
Gene expression profile analysis of Drosophila melanogaster selected for resistance to environmental stressors.
Sample Metadata Fields
No sample metadata fields
View Samples- Arabidopsis thaliana
- 12 Downloadable Samples
- Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)
Description
Transcriptional variation, also called expression level polymorphism (ELP), contributes to intra-specific phenotypic variation in many organisms. Differentially expressed transcripts are typically enriched for stress-related genes, suggesting that differences in response to the environment are a particularly common point of divergence among gentoypes. Analysis of ELPs also has been suggested as a way to assess unintended consequences of transgene introduction; however, it is important that interpretation of transcriptional changes be performed within the context of potential fitness effects. In these studies we sought to examine differential gene expression in response to salinity for two widely used Arabidopsis thaliana ecotypes, Wassilewskija (Ws) and Columbia (Col), and a single gene mutation (glabrous, gl1-1) in the Col background (Col(gl)), in relation to genetic, phenotypic, and fitness differences.
Publication Title
Global gene expression analysis of transgenic, mannitol-producing, and salt-tolerant Arabidopsis thaliana indicates widespread changes in abiotic and biotic stress-related genes.
Sample Metadata Fields
Age, Specimen part
View Samples- Arabidopsis thaliana
- 8 Downloadable Samples
- Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)
Description
Mannitol is a putative osmoprotectant contributing to salt tolerance in several species. Arabidopsis plants transformed with the mannose-6-phosphate reductase (M6PR) gene from celery were dramatically more salt tolerant (at 100mM NaCl) as exhibited by reduced salt injury, less inhibition of vegetative growth, and increased seed production relative to the wild type (WT). When treated with 200mM NaCl, transformants produced no seeds, but did bolt, and exhibited less chlorosis/necrosis and greater survival and dry weights than the WT. Without salt there were no M6PR effects on growth or phenotype, but expression levels of 2272 genes were altered. Many fewer differences (1039) were observed between M6PR and WT plants in the presence of salt, suggesting that M6PR pre-conditioned the plants to stress. Previous work suggested that mannitol is an osmoprotectant, but mannitol levels are invariably quite low, perhaps inadequate for osmoprotectant effects. In this study, transcriptome analysis reveals that the M6PR transgene activated the downstream abscisic acid (ABA) pathway by up-regulation of ABA receptor genes (PYL4, PYL5, and PYL6) and down-regulation of protein phosphatase 2C genes (ABI1 and ABI2). In the M6PR transgenic lines there were also increases in transcripts related to redox and cell wall-strengthening pathways. These data indicate that mannitol-enhanced stress tolerance is due at least in part to increased expression of a variety of stress-inducible genes.
Publication Title
Global gene expression analysis of transgenic, mannitol-producing, and salt-tolerant Arabidopsis thaliana indicates widespread changes in abiotic and biotic stress-related genes.
Sample Metadata Fields
Age, Specimen part
View Samples- Arabidopsis thaliana
- 24 Downloadable Samples
- Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)
Description
Engineered abiotic stress resistance is an important target for increasing agricultural productivity.There are concerns, however, regarding possible ecological impacts of transgenic crops. In contrast to the first wave of transgenic crops, many abiotic stress resistance genes can initiate
Publication Title
Comparison of salt stress resistance genes in transgenic Arabidopsis thaliana indicates that extent of transcriptomic change may not predict secondary phenotypic or fitness effects.
Sample Metadata Fields
Age, Specimen part, Treatment
View Samples- Drosophila melanogaster
- 24 Downloadable Samples
- Affymetrix Drosophila Genome 2.0 Array (drosophila2)
Description
We used microarrays to investigate the transcriptome of 6 days old male flies exposed to either 15 or 25 C development at either constant or fluctuating temperatures. Further, we investigated gene expression at benign (20C) and high (35C) temperatures
Publication Title
Thermal fluctuations affect the transcriptome through mechanisms independent of average temperature.
Sample Metadata Fields
Sex
View Samples- Drosophila melanogaster
- 36 Downloadable Samples
- Affymetrix Drosophila Genome Array (drosgenome1)
Description
gene expression was measured in control and heat resistance selected adult female flies before and at 8 time points after heat stress for 1h @ 36 degrees
Publication Title
Full genome gene expression analysis of the heat stress response in Drosophila melanogaster.
Sample Metadata Fields
No sample metadata fields
View Samples- Drosophila melanogaster
- 10 Downloadable Samples
- Affymetrix Drosophila Genome Array (drosgenome1)
Description
gene expression was measured in five independent heat resistance selected replicate lines and five control lines.
Publication Title
Full genome gene expression analysis of the heat stress response in Drosophila melanogaster.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 26 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
The purpose of this study was to characterize the histologic development of OA in a mouse model where OA is induced by destabilization of the medial meniscus (DMM model) and to identify genes regulated during different stages of the disease, using RNA isolated from the joint organ and analyzed using microarrays.427 genes from the microarrays passed consistency and significance filters. There was an initial up-regulation at 2 and 4 weeks of genes involved in morphogenesis, differentiation, and development, including growth factor and matrix genes, as well as transcription factors including Atf2, Creb3l1, and Erg. Most genes were off or down-regulated at 8 weeks with the most highly down-regulated genes involved in cell division and the cytoskeleton. Gene expression increased at 16 weeks, in particular extracellular matrix genes including Prelp, Col3a1 and fibromodulin.The results support a phasic development of OA with early matrix remodelling and transcriptional activity followed by a more quiescent period that is not maintained.
Publication Title
Disease progression and phasic changes in gene expression in a mouse model of osteoarthritis.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples