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SRP042112
Homo sapiens
9 Downloadable Samples
IonTorrentProton
Description
Schizophrenia and other psychiatric disorders are postulated to be developmental disorders resulting from synapse dysfunction. How susceptibility genes for major mental disorders could lead to synaptic deficits in humans is not well-understood. Here we generated induced pluripotent stem cells (iPSCs) from four members of a family in which a frame-shift mutation of Disrupted-in-schizophrenia-1 (DISC1) co-segregated with psychiatric disorders and further produced different isogenic iPSC lines via genetic editing. We showed that mutant DISC1 causes synaptic vesicle release deficits in iPSC-derived forebrain neurons. Mechanistically, mutant DISC1 dysregulates the expression of many genes related to synapses and psychiatric disorders and depletes wild-type DISC1 and the NCoR1 transcription co-repressor complex. Furthermore, mechanism-guided pharmacological inhibition of phosphodiesterases rescues synaptic defects in mutant neurons. Our study uncovers a novel gain-of-function mechanism through which the psychiatric disorder-relevant mutation affects synaptic functions via transcriptional dysregulation and provides insight into the molecular and synaptic etiopathology of psychiatric disorders. Overall design: Two patient derived iPSC lines carrying heterozygous 4bp deletion in DISC1 gene and 1 related control were analyzed in biological triplicate
Publication Title
Synaptic dysregulation in a human iPS cell model of mental disorders.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 20 Downloadable Samples
- Illumina HiSeq 2000
Description
Cerebral organoids, three-dimensional cultures that model organogenesis, provide a new platform to investigate human brain development. High cost, variability and tissue heterogeneity limit accessibility and broad applications of current organoid technologies. Here we developed a miniaturized spinning bioreactor (SpinO) to generate forebrain-specific organoids from human iPSCs. These organoids recapitulate key features of human cortical development, including progenitor zone organization, neurogenesis, gene expression, and importantly, a distinct human-specific outer radial glia cell layer. We have also developed protocols to generate midbrain and hypothalamic organoids. Finally, we employed this forebrain organoid platform to model Zika virus (ZIKV) exposure. Quantitative analyses revealed that preferential, productive ZIKA infection of cortical neural progenitors leads to increased cell death and reduced proliferation, resulting in decreased neuronal cell layer volume that resembles microcephaly. Together, our brain region-specific organoids and SpinO provide an accessible and versatile platform for modeling human brain development and diseases, and for compound testing. Overall design: Time course of human cerebral organoid cultures. No Zika virus infection is involved.
Publication Title
Brain-Region-Specific Organoids Using Mini-bioreactors for Modeling ZIKV Exposure.
Sample Metadata Fields
Subject, Time
View Samples- Mus musculus
- 4 Downloadable Samples
- Illumina HiSeq 2000
Description
We report that cellular ROS enzymatically generated in response to contact with lactobacilli in both mice and Drosophila has salutary effects against exogenous insults to the intestinal epithelium via the activation of Nrf2 responsive cytoprotective genes. Overall design: RNA was isolated from the colons of untreated, PBS, E. coli, and LGG innoculated germ free mice and RNA-seq performed to identify the gene expression in response to each condition
Publication Title
Lactobacillus rhamnosus GG-induced Expression of Leptin in the Intestine Orchestrates Epithelial Cell Proliferation.
Sample Metadata Fields
Age, Specimen part, Cell line, Subject
View Samples- Mus musculus
- 54 Downloadable Samples
- Illumina HiSeq 2500
Description
Dose-dependent femoral gene expression was examined following repeated exposure (every 4 days for 28 days) to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). These data were used to examine the effect of repeated TCDD exposure on gene expression in the femur of C57BL/6 male mice. Overall design: Three biological replicates for each dose (0.01, 0.03, 0.1, 0.3, 1, 3, 10, 30) of TCDD and sesame oil vehicle
Publication Title
2,3,7,8-Tetrachlorodibenzo-p-dioxin dose-dependently increases bone mass and decreases marrow adiposity in juvenile mice.
Sample Metadata Fields
Sex, Specimen part, Cell line, Treatment, Subject
View Samples- Mus musculus
- 54 Downloadable Samples
- Illumina HiSeq 2500
Description
Dose-dependent ileal gene expression was examined following repeated exposure (every 4 days for 28 days) to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). These data were used to examine the effect of repeated TCDD exposure on gene expression in the intestinal epithelium of C57BL/6 male mice. Overall design: Three biological replicates for each dose (0.01, 0.03, 0.1, 0.3, 1, 3, 10, 30) of TCDD and sesame oil vehicle
Publication Title
2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD)-elicited effects on bile acid homeostasis: Alterations in biosynthesis, enterohepatic circulation, and microbial metabolism.
Sample Metadata Fields
Sex, Cell line, Treatment, Subject
View Samples- Mus musculus
- 54 Downloadable Samples
- Illumina HiSeq 2500
Description
Dose-dependent duodenal gene expression was examined following repeated exposure (every 4 days for 28 days) to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). These data were used to examine the effect of repeated TCDD exposure on gene expression in the intestinal epithelium of C57BL/6 male mice. Overall design: Three biological replicates for each dose (0.01, 0.03, 0.1, 0.3, 1, 3, 10, 30) of TCDD and sesame oil vehicle
Publication Title
Convergence of hepcidin deficiency, systemic iron overloading, heme accumulation, and REV-ERBα/β activation in aryl hydrocarbon receptor-elicited hepatotoxicity.
Sample Metadata Fields
Sex, Specimen part, Cell line, Treatment, Subject
View Samples- Mus musculus
- 54 Downloadable Samples
- Illumina HiSeq 2500
Description
Dose-dependent hepatic gene expression was examined following repeated exposure (every 4 days for 28 days) to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). These data were used to examine the effect of repeated TCDD exposure on gene expression in the liver of C57BL/6 male mice. Overall design: Three biological replicates for each dose (0.01, 0.03, 0.1, 0.3, 1, 3, 10, 30) of TCDD and sesame oil vehicle
Publication Title
Convergence of hepcidin deficiency, systemic iron overloading, heme accumulation, and REV-ERBα/β activation in aryl hydrocarbon receptor-elicited hepatotoxicity.
Sample Metadata Fields
Sex, Specimen part, Cell line, Treatment, Subject
View Samples- Homo sapiens
- 6 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The HT29 derivative cell line HT29-MTX-E12 (E12) produces an adherent mucus layer predominantly of the gastric MUC5AC mucin when grown on transwells. This mucus layer supports Helicobacter pylori survival in culture. E12 cells were infected with H. pylori and the transcriptome of infected and uninfected E12 were compared. Also included for comparison was the HT29 parent cell line grown on transwells.
Publication Title
Glycosylation-related gene expression in HT29-MTX-E12 cells upon infection by <i>Helicobacter pylori</i>.
Sample Metadata Fields
Cell line
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Fetal liver of E14.5 RNaseh2b KOF and Rnaseh2b wild type embryos was isolated, RNA was extracted and microarray analysis using Affymetrix Mouse 430 2.0 gene chip was performed
Publication Title
Mammalian RNase H2 removes ribonucleotides from DNA to maintain genome integrity.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 28 Downloadable Samples
- Affymetrix Mouse Genome 430A 2.0 Array (mouse430a2)
Description
Ag recognition via the TCR is necessary for the expansion of specific T cells that then contribute to adaptive immunity as effector and memory cells. Because CD4+ and CD8+ T cells differ in terms of their priming APCs and MHC ligands we compared their requirements of Ag persistence during their expansion phase side by side. Proliferation and effector differentiation of TCR transgenic and polyclonal mouse T cells were thus analyzed after transient and continuous TCR signals. Following equally strong stimulation, CD4+ T cell proliferation depended on prolonged Ag presence, whereas CD8+ T cells were able to divide and differentiate into effector cells despite discontinued Ag presentation. CD4+ T cell proliferation was neither affected by Th lineage or memory differentiation nor blocked by coinhibitory signals or missing inflammatory stimuli. Continued CD8+ T cell proliferation was truly independent of self-peptide/MHC-derived signals. The subset divergence was also illustrated by surprisingly broad transcriptional differences supporting a stronger propensity of CD8+ T cells to programmed expansion. These T cell data indicate an intrinsic difference between CD4+ and CD8+ T cells regarding the processing of TCR signals for proliferation. We also found that the presentation of a MHC class IIrestricted peptide is more efficiently prolonged by dendritic cell activation in vivo than a class I bound one. In summary, our data demonstrate that CD4+ T cells require continuous stimulation for clonal expansion, whereas CD8+ T cells can divide following a much shorter TCR signal.
Publication Title
Differential kinetics of antigen dependency of CD4+ and CD8+ T cells.
Sample Metadata Fields
Specimen part, Treatment
View Samples