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SRP091374
Mus musculus
6 Downloadable Samples
Illumina HiSeq 2500
Description
Autism spectrum disorders (ASD) are a group of genetic disorders often overlapping with other neurological conditions. We previously described abnormalities in the branched chain amino acid (BCAA) catabolic pathway as a cause of ASD. Here we show that the solute carrier transporter 7a5 (SLC7A5), a large neutral amino acid transporter localized at the blood brain barrier (BBB), has an essential role in maintaining normal levels of brain BCAAs. In mice, deletion of Slc7a5 from the endothelial cells of the BBB leads to decreased levels of brain BCAAs, abnormal mRNA translation and severe neurological abnormalities. Furthermore, we identified several patients with autistic traits and motor delay carrying deleterious homozygous mutations in the SLC7A5 gene. Finally, we demonstrate that BCAA intracerebroventricular administration ameliorates abnormal behaviors in adult mutant mice. Our data elucidate a neurological syndrome defined by SLC7A5 mutations and support an essential role for the BCAA in human brain function. Overall design: RNA-sequencing of cerebellum from 3 wildtype mice and 3 Slc7a5 KO mice
Publication Title
Impaired Amino Acid Transport at the Blood Brain Barrier Is a Cause of Autism Spectrum Disorder.
Sample Metadata Fields
Specimen part, Subject
View Samples- Arabidopsis thaliana
- 30 Downloadable Samples
Affymetrix Arabidopsis Genome Array (ag)
Description
Analysis of gene expression in Ws-0 lec1 (LEAFY COTYLEDON1) mutant Arabidopsis thaliana. Developmental stages studied includes 24-Hr post-fertilization, globular stage, cotyledon stage, mature green stage, post-mature green stage, and seedlings.
Publication Title
LEC1 sequentially regulates the transcription of genes involved in diverse developmental processes during seed development.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 114 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
We report genomic analysis of 300 meningiomas, the most common primary brain tumors, leading to the discovery of mutations in TRAF7, a proapoptotic E3 ubiquitin ligase, in nearly one-fourth of all meningiomas. Mutations in TRAF7 commonly occurred with a recurrent mutation (K409Q) in KLF4, a transcription factor known for its role in inducing pluripotency, or with AKT1(E17K), a mutation known to activate the PI3K pathway. SMO mutations, which activate Hedgehog signaling, were identified in ~5% of non-NF2 mutant meningiomas. These non-NF2 meningiomas were clinically distinctive-nearly always benign, with chromosomal stability, and originating from the medial skull base. In contrast, meningiomas with mutant NF2 and/or chromosome 22 loss were more likely to be atypical, showing genomic instability, and localizing to the cerebral and cerebellar hemispheres. Collectively, these findings identify distinct meningioma subtypes, suggesting avenues for targeted therapeutics.
Publication Title
Genomic analysis of non-NF2 meningiomas reveals mutations in TRAF7, KLF4, AKT1, and SMO.
Sample Metadata Fields
Disease stage
View Samples- Homo sapiens
- 7 Downloadable Samples
- IlluminaHiSeq2000
Description
Neuronal migration defects (NMDs) are among the most common and severe brain abnormalities in humans. Lack of disease models in mice or in human cells has hampered the identification of underlying mechanisms. From patients with severe NMDs we generated iPSCs then differentiated neural progenitor cells (NPCs). On artificial extracellular matrix, patient-derived neuronal cells showed defective migration and impaired neurite outgrowth. From a cohort of 107 families with NMDs, sequencing identified two homozygous C-terminal truncating mutations in CTNNA2, encoding aN-catenin, one of three paralogues of the a-catenin family, involved in epithelial integrity and cell polarity. Patient-derived or CRISPR-targeted CTNNA2- mutant neuronal cells showed defective migration and neurite stability. Recombinant aN-catenin was sufficient to bundle purified actin and to suppress the actin-branching activity of ARP2/3. Small molecule inhibitors of ARP2/3 rescued the CTNNA2 neurite defect. Thus, disease modeling in human cells could be used to understand NMD pathogenesis and develop treatments for associated disorders. Overall design: 2 biological replicates per individual (2 iPSC clone differentiations), excluding 1263A, which has one sample
Publication Title
Biallelic loss of human CTNNA2, encoding αN-catenin, leads to ARP2/3 complex overactivity and disordered cortical neuronal migration.
Sample Metadata Fields
No sample metadata fields
View Samples- Drosophila melanogaster
- 6 Downloadable Samples
- Affymetrix Drosophila Genome 2.0 Array (drosophila2)
Description
Examined the expression effects of supplementing Drosophila food on heart and nephrocyte complexes
Publication Title
Diet-Induced Podocyte Dysfunction in Drosophila and Mammals.
Sample Metadata Fields
Sex, Specimen part, Treatment
View Samples- Drosophila melanogaster
- 9 Downloadable Samples
- Drosophila Gene 1.0 ST Array (drogene10st)
Description
Mitochondrial DNA (mtDNA) encodes essential components of the respiratory chain and loss of mtDNA leads to mitochondrial dysfunction and neurodegeneration. Mitochondrial transcription factor A (TFAM) is an essential component of mtDNA replication and a regulator of mitochondrial copy number in cells. Studies have shown that TFAM knockdown leads to mitochondrial dysfunction and respiratory chain deficiencies. ATP synthase is Complex V of the mitochondrial respiratory chain. It is driven by a proton gradient between the intermembrane space and the mitochondrial matrix and generates the majority of cellular ATP. The knockdown of coupling factor 6 (Cf6), one of the components of the proton channel F0, causes dysfunction in the complex, leading to mitochondrial dysfunction and respiratory chain deficiencies. Using gene expression analysis, we aimed to investigate the effects of mtDNA dysfunction in the CNS at the molecular level.
Publication Title
Mitochondrial retrograde signaling regulates neuronal function.
Sample Metadata Fields
Specimen part
View Samples- Drosophila melanogaster
- 11 Downloadable Samples
- Affymetrix Drosophila Genome 2.0 Array (drosophila2)
Description
Chronic high sugar feeding induces obesity, hyperglycemia, and insulin resistance in flies and mammals. To gain insight into the mechanisms underlying this response, we profiled gene expression in chronically high sugar fed, wandering (post-prandial) third instar wild type larvae (L3). These data were compared to control-fed larvae as well as those (mid-L3) actively feeding for twelve hours on both diets.
Publication Title
A high-sugar diet produces obesity and insulin resistance in wild-type Drosophila.
Sample Metadata Fields
Sex, Specimen part
View Samples- Drosophila melanogaster
- 9 Downloadable Samples
- Affymetrix Drosophila Genome Array (drosgenome1)
Description
Expression profiles of wild type migratory border cells (WTBC), non-migrating slbo mutant border cells (slboBC) and non-migrating follicle cells (FC)
Publication Title
Systematic analysis of the transcriptional switch inducing migration of border cells.
Sample Metadata Fields
Sex, Specimen part
View Samples- Arabidopsis thaliana
- 15 Downloadable Samples
- Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)
Description
We generated single and double knockouts of AtNHX5 and AtNHX6 in order to invesigate possible functions in Arabidopsis. nhx5/nhx6 exhibited severe growth retardation related to cell size and proliferation, as well as endosomal trafficking perutrbations. The results implicate endosomal NHX antiporters in novel cellular functions. In order to investigate further the possible functions of AtNHX5 and AtNHX6, we compared the transcrptional profiles of single and double AtNHX5 and AtNHX6 knockouts. We looked for changes in gene expression might help us to elucidate the molecular events associated with the apparent requirement of AtNHX5 and AtNHX6 for normal growth and development.
Publication Title
The Arabidopsis intracellular Na+/H+ antiporters NHX5 and NHX6 are endosome associated and necessary for plant growth and development.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 12 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
The exposure to and contamination by Persistent Organic Pollutants (POPs), which include pesticides used worldwide and polyaromatic hydrocarbons, is detrimental to human health and diverse ecosystems. Although most mechanistic studies have focused on single compounds, living organisms are exposed to multiple environmental xenobiotics, simultaneously, throughout their lives. The experimental evidence useful for assessing the effects of exposure to pollutant mixtures is scarce. We investigated the effects of exposure to a combination of two POPs, which employ different xenosensors, on global gene expression in a human hepatocyte cell model, HepaRG.
Publication Title
Two persistent organic pollutants which act through different xenosensors (alpha-endosulfan and 2,3,7,8 tetrachlorodibenzo-p-dioxin) interact in a mixture and downregulate multiple genes involved in human hepatocyte lipid and glucose metabolism.
Sample Metadata Fields
Specimen part
View Samples