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SRP055084
Mus musculus
4 Downloadable Samples
Illumina HiSeq 2000
Description
Purpose: Two secreted Toxoplasma proteins (GRA17 and GRA23) mediate the passage of small molecules between the host cytoplasm and the parasite-containing vacuole. This provides the first molecular explanation to how intracellular, vacuole-residing parasites in the phylum Apicomplexa, like Plasmodium, gain access to host nutrients. Methods: Mouse-derived Bone Marrow Macrophages were infected with Toxoplasma tachyzoites of either WT, dGRA17, dGRA23, or dGRA17rescue genetic background for 4 hours. Results: GRA23 gene expression levels are elevated in the dGRA17 strain but not vice versa. Conclusions: GRA17 and GRA23 are synergistically required for permeability of small molecules into the Toxoplasma parasitophorous vacuole. Overall design: Toxoplasma and Mouse gene expression profiles from BMDMs infected with either WT (control), dGRA17, gGRA23, or dGRA17rescue (control) tachyzoites were obtained by RNA-Seq on an Illumina HiSeq2000 instruments at 4 hours post-infection.
Publication Title
The Toxoplasma Dense Granule Proteins GRA17 and GRA23 Mediate the Movement of Small Molecules between the Host and the Parasitophorous Vacuole.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 79 Downloadable Samples
Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Weve undertaken a genome-wide approach to identify and test genes in fibroblasts that are both induced upon interaction with basal breast cancer cells in culture and upregulated in stromal cells from primary human breast cancers. Several of the upregulated genes encode secreted growth factors or cytokines. Using RNAi and a co-injection tumorigenicity assay, we determined that the majority of secreted factors selected for functional validation played significant, yet functionally diverse, roles in promoting tumorigenicity. Rather than a single major mediator, these results indicate multiple points of intervention to prevent fibroblasts from supporting basal breast cancer. Additionally, we show that breast cancer subtypes differ markedly in the expression of these and other stromally secreted proteins using data from microdissected stromal samples.
Publication Title
System-wide analysis reveals a complex network of tumor-fibroblast interactions involved in tumorigenicity.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Quercetin has been described to have a wide range of beneficial effects in humans, ranging from anti-carcinogenic properties to reduced risk of cardiovascular disease. We tested whether a daily supplementation of quercetin leads to reproducible changes in gene expression profiles of human monocytes.
Publication Title
Quercetin supplementation and its effect on human monocyte gene expression profiles in vivo.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 25 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Fibroblasts from patients with Type I bipolar disorder (BPD) and their unaffected siblings were obtained from an Old Order Amish pedigree with a high incidence of BPD and reprogrammed to induced pluripotent stem cells (iPSCs). Established iPSCs were subsequently differentiated into neuroprogenitors (NPs) and then to neurons. Transcriptomic microarray analysis was conducted on RNA samples from iPSCs, NPs and neurons matured in culture for either 2 weeks (termed early neurons, E) or 4 weeks (termed late neurons, L). Global RNA profiling indicated that BPD and control iPSCs differentiated into NPs and neurons at a similar rate, enabling studies of differentially expressed genes in neurons from controls and BPD cases. Significant disease-associated differences in gene expression were observed only in L neurons. Specifically, 328 genes were differentially expressed between BPD and control L neurons including GAD1, glutamate decarboxylase 1 (2.5 fold) and SCN4B, the voltage gated type IV sodium channel beta subunit (-14.6 fold). Quantitative RT-PCR confirmed the up-regulation of GAD1 in BPD compared to control L neurons. Gene Ontology, GeneGo and Ingenuity Pathway Analysis of differentially regulated genes in L neurons suggest that alterations in RNA biosynthesis and metabolism, protein trafficking as well as receptor signaling pathways GSK3 signaling may play an important role in the pathophysiology of BPD.
Publication Title
Transcriptomic Analysis of Induced Pluripotent Stem Cells Derived from Patients with Bipolar Disorder from an Old Order Amish Pedigree.
Sample Metadata Fields
Specimen part, Disease, Disease stage
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
The amyloid precursor protein (APP) plays a central role in the pathogenesis of Alzheimers disease (AD). Processing of APP by - and -secretase activities results in the production of -amyloid (A), the main constituent of Alzheimer plaques, but also in the generation of the APP intracellular domain (AICD). Recently, it has been demonstrated that AICD has transactivation potential, however, the targets of AICD dependent gene regulation and hence the physiological role of AICD remain largely unknown. In this work we analysed transcriptome changes during AICD dependent gene regulation using a human neural cell culture system inducible for expression of AICD, its co-activator Fe65, or the combination of both. Induction of AICD was associated with increased expression of genes with known function in the organization and dynamics of the actin cytoskeleton as well as genes involved in the regulation of apoptosis.
Publication Title
Modulation of gene expression and cytoskeletal dynamics by the amyloid precursor protein intracellular domain (AICD).
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 16 Downloadable Samples
- Affymetrix Human Gene 1.1 ST Array (hugene11st)
Description
Different fibroblast cells (eight in total) with different inhibitory capacity were analyzed and compared for their gene expression profile by whole genome microarray.
Publication Title
Confrontation of fibroblasts with cancer cells in vitro: gene network analysis of transcriptome changes and differential capacity to inhibit tumor growth.
Sample Metadata Fields
Cell line, Treatment
View Samples- Mus musculus
- 10 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
We established a mouse model, in which transcription factor Tcfap2c can be activated in an inducible and reversible manner in somatic tissues, taking advantage of the tetracycline-dependent regulatory system.
Publication Title
Transgenic overexpression of Tcfap2c/AP-2gamma results in liver failure and intestinal dysplasia.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 23 Downloadable Samples
- Illumina HiSeq 2000
Description
Genome-wide analyses have identified thousands of long non-coding RNAs (lncRNAs). Malat1 (Metastasis Associated Lung Adenocarcinoma Transcript 1) is among the most abundant lncRNAs whose expression is altered in numerous cancers. Here we report that genomic loss, as well as systemic knockdown of Malat1 using antisense oligonucleotides, in the MMTV-PyMT mouse mammary carcinoma model results in slower tumor growth accompanied by differentiation into highly cystic tumors and a significant reduction in lung metastasis. Further, Malat1 loss results in a reduction of branching morphogenesis in MMTV-PyMT and Her2/neu amplified tumor organoids consistent with the in vivo reduction in lung metastasis. At the molecular level, Malat1 knockdown results in alterations in gene expression and changes in splicing patterns of genes involved in differentiation and pro-tumorigenic signaling pathways. Together, these data indicate that the lncRNA Malat1 regulates critical processes in mammary cancer pathogenesis and represents a promising therapeutic target for inhibiting breast cancer metastasis. Overall design: Transcriptome profiles of tumors and organoids after Malat1 knockdown using antisense olgonucleotides (ASOs).
Publication Title
Differentiation of mammary tumors and reduction in metastasis upon Malat1 lncRNA loss.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 4 Downloadable Samples
- Affymetrix Human Genome U219 Array (hgu219)
Description
LMO2 overexpressing transgenic mouse models suggest an accumulation of immature T-cell progenitors in the thymus as main pre-leukemic event. The effects of LMO2 overexpression on human T-cell development in vivo, however, are unknown. Here we report studies of a humanized mouse model transplanted with LMO2 transduced human hematopoietic stem and progenitor cells. The effects of LMO2 overexpression were confined to the T-cell lineage although initially multipotent cells were transduced. Three effects of LMO2 on human T-cell development were observed: 1) a block at the DN/ISP stage, 2) an accumulation of CD4+CD8+ double positive CD3- cells and 3) an altered CD8/CD4 ratio with enhanced peripheral T lymphocytes
Publication Title
Overexpression of LMO2 causes aberrant human T-Cell development in vivo by three potentially distinct cellular mechanisms.
Sample Metadata Fields
Specimen part
View Samples- Rattus norvegicus
- 83 Downloadable Samples
- IlluminaHiSeq2500
Description
Rapalogs, inhibitors of mTORC1 (mammalian target of rapamycin complex 1), increase life span and delay age-related phenotypes in many species. However, the molecular mechanisms have not been fully elucidated. We determined gene expression changes comparing 6- and 24-month-old rats in the kidney, liver, and skeletal muscle, and asked which of these changes were counter-regulated by a clinically-translatable (short-term and low-concentration) treatment, with a rapalog (RAD001). Surprisingly, RAD001 had a more pronounced effect on the kidney under this regimen in comparison to the liver or skeletal muscle. Histologic evaluation of kidneys revealed that the severity of chronic progressive nephropathy lesions was lower in kidneys from 24-month-old rats treated with RAD001 compared with vehicle. In addition to other gene expression changes, c-Myc, which has been shown to regulate aging, was induced by aging in the kidney and counter-regulated by RAD001. RAD001 caused a decrease in c-Myc protein, which could be rescued by a proteasome inhibitor. These findings point to settings for use of mTORC1 inhibitors to treat age-related disorders, and highlight c-Myc regulation as one of the potential mechanisms by which mTORC1 inhibition is perturbing age-related phenotypes. Overall design: Transcriptional profiling was performed in kidney, liver and gastrocnemius muscles from three experimental groups of male Sprague Dawley rats. Rats aged 4.5 month (m) and 22.5 m were treated with vehicle and rats aged 22.5 m were treated with RAD001 for 6 weeks, with a read-out at 6 and 24 months.
Publication Title
Short-term Low-Dose mTORC1 Inhibition in Aged Rats Counter-Regulates Age-Related Gene Changes and Blocks Age-Related Kidney Pathology.
Sample Metadata Fields
No sample metadata fields
View Samples