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Mus musculus
12 Downloadable Samples
Affymetrix Mouse Expression 430A Array (moe430a)
Description
The murine model of Lyme disease provides a unique opportunity to study the localized host response to similar stimulus, B. burgdorferi, in the joints of mice destined to develop severe arthritis (C3H) or mild disease (C57BL/6). Pathways associated with the response to infection and the development of Lyme arthritis were identified by global gene expression patterns using oligonucleotide microarrays. A robust induction of IFN responsive genes was observed in severely arthritic C3H mice at one week of infection, which was absent from mildly arthritic C57BL/6 mice. In contrast, infected C57BL/6 mice displayed a novel expression profile characterized by genes involved in epidermal differentiation and wound repair, which were decreased in the joints of C3H mice. These expression patterns were associated with disease state rather than inherent differences between C3H and C57BL/6 mice, as C57BL/6-IL10-/- mice infected with B. burgdorferi develop more severe arthritis that C57BL/6 mice and displayed an early gene expression profile similar to C3H mice. Gene expression profiles at two and four weeks post infection revealed a common response of all strains that was likely to be important for the host defense to B. burgdorferi and mediated by NF-kB-dependent signaling. The gene expression profiles identified in this study add to the current understanding of the host response to B. burgdorferi and identify two novel pathways that may be involved in regulating the severity of Lyme arthritis.
Publication Title
Gene expression profiling reveals unique pathways associated with differential severity of lyme arthritis.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 10 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Gene expression profile of joint tissue from C3H and interval specific congenic mouse lines (ISCL) following infection with Borrelia burgdorferi
Publication Title
Interval-specific congenic lines reveal quantitative trait Loci with penetrant lyme arthritis phenotypes on chromosomes 5, 11, and 12.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 23 Downloadable Samples
Illumina HiSeq 2000
Description
T lymphocytes are essential contributors to the adaptive immune system and consist of multiple lineages that serve various effector and regulatory roles. As such, precise control of gene expression is essential to the proper development and function of these cells. Previously, we identified Snai2 and Snai3 as being essential regulators of immune tolerance partly due to the impaired function of CD4+ regulatory T cells in Snai2/3 conditional double knockout mice. Here we extend those previous findings using a bone marrow transplantation model to provide an environmentally unbiased view of the molecular changes imparted onto various T lymphocyte populations once Snai2 and Snai3 are deleted. The data presented here demonstrate that Snai2 and Snai3 transcriptionally regulate the cellular fitness and functionality of not only CD4+ regulatory T cells but effector CD8a+ and CD4+ conventional T cells as well. This is achieved through the modulation of gene sets unique to each cell type and includes transcriptional targets relevant to the survival and function of each T cell lineage. As such, Snai2 and Snai3 are essential regulators of T cell immunobiology. Overall design: GFP- CD3e+ CD8a+ CD4-, GFP- CD3e+ CD8a- CD4+ CD25- and GFP- CD3e+ CD8a- CD4+ CD25+ T cells were isolated from spleens of UBC-GFP mice transplanted with WT or cDKO lineage-depleted donor bone marrow following lethal irradiation of recipient mice. RNA-seq was performed on 3-4 biological replicates from each genotype for all T cell populations analyzed.
Publication Title
Snai2 and Snai3 transcriptionally regulate cellular fitness and functionality of T cell lineages through distinct gene programs.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Homo sapiens
- 12 Downloadable Samples
- Illumina HiSeq 2000
Description
Mucinous tubular and spindle cell carcinoma (MTSCC) is a relatively rare subtype of renal cell carcinoma with distinctive morphologic and cytogenetic features. Here we carry out whole exome and transcriptome sequencing of a multi-institutional cohort of MTSCC (n=22). We demonstrate the presence of either biallelic loss of Hippo pathway tumor suppressor genes (TSGs) and/or evidence of alteration of Hippo pathway genes in 85% of samples. PTPN14 (31%) and NF2 (22%) were the most commonly implicated Hippo pathway genes while other genes such as SAV1 and HIPK2 were also involved in a mutually exclusive fashion. Mutations in the context of recurrent chromosomal losses amounted to bi-allelic alterations in these TSGs. As a read-out of Hippo pathway inactivation, a majority of cases (90%) exhibited increased nuclear YAP1 protein expression. To identify transcriptional targets of the Hippo pathway in kidney we performed PTPN14 knockdown followed by RNA-seq in 2 kidney cancer cell lines (CAKI-1 and A-704) and a normal kidney epithelial cell line (HK-2). PTPN14 siRNAs were first functionally validated in a MCF-7 TEAD reporter luciferase stable cell line. Both siRNAs showed comparable knockdown efficiency and significantly increased luciferase reporter activity. In 2 of the kidney cell lines PTPN14 knockdown increased cell proliferation compared to non-target controls. While we observed excellent correlation between genes dysregulated by either PTPN14 or LATS1 knockdown within each cell line (HK2, CAKI-1 and A704), the overlap across the 3 cell lines was only 23 genes. Further, these 23 genes did not show concordant differential expression in MTSCC tumors. Overall, these results illustrate the marked tissue specificity of Hippo pathway targets.Finally, taken together, nearly all cases of MTSCC exhibit some evidence of Hippo pathway dysregulation. Overall design: Cell lines (CAKI-1, HK2 or A704) were either transfected with 2 independent siRNAs or non-target controls. Forty eight hours post transcription total RNA was isolated and subjected to RNA-seq analysis
Publication Title
Biallelic Alteration and Dysregulation of the Hippo Pathway in Mucinous Tubular and Spindle Cell Carcinoma of the Kidney.
Sample Metadata Fields
Specimen part, Disease, Disease stage, Cell line, Subject
View Samples
GSE30747- Mus musculus
- 28 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
An integrated approach to dissecting oncogene addiction implicates a Myb-coordinated self-renewal program as essential for leukemia maintenance.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Mus musculus
- 16 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
To explore oncogene addiction programs in a genetically defined leukemia context we developed an AML mouse model driven by a conditional MLL-AF9 allele together with oncogenic Ras, which enabled us to examine the consequences of MLL-AF9 inhibition in established disease. In order to produce a tightly regulated system that was easy to monitor, we constructed two retroviral vectors containing dsRed-linked MLL-AF9 under control of a tetracycline response element promoter, and KrasG12D or NrasG12D linked to the Tet-off tet-transactivator, which activates TRE expression in a doxycycline repressible manner. Leukemias were generated by retroviral cotransduction of both vectors into hematopoietic stem and progenitor cells, which were transplanted into syngeneic mice. Cells harboring both constructs induced aggressive myelomonocytic leukemia. Five independent primary leukemia cell lines were established from bone marrow of terminal mice. Treatment of these lines with doxycycline rapidly turned off MLL-AF9 expression, and induced terminal myeloid differentiation and complete disease remission in vivo.
Publication Title
An integrated approach to dissecting oncogene addiction implicates a Myb-coordinated self-renewal program as essential for leukemia maintenance.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Using an integrative approach combining a Tet-off conditional AML mouse model, global expression profiling following suppression of the driving MLL-AF9 oncogene, and a new Tet-on conditional shRNA expression system we have identified Myb as critical mediator of addiction to MLL-AF9. Suppression of Myb in established AML in vivo terminates aberrant self-renewal and triggers a terminal myeloid differentiation program that precisely phenocopies the effects of suppressing MLL-AF9. Remarkably, suppressing Myb effectively eradicates aggressive and chemotherapy resistant AML.
Publication Title
An integrated approach to dissecting oncogene addiction implicates a Myb-coordinated self-renewal program as essential for leukemia maintenance.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 209 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
A genome-wide RNA expression study based on a Phase II randomized placebo-controlled clinical trial of topiramate (TPM) treatment of methamphetamine (METH) dependence.
Publication Title
Transcriptome profiling and pathway analysis of genes expressed differentially in participants with or without a positive response to topiramate treatment for methamphetamine addiction.
Sample Metadata Fields
Sex, Age, Specimen part, Treatment, Race, Subject, Time
View Samples- Mus musculus
- 12 Downloadable Samples
- Illumina HiSeq 2000
Description
RNA seq analysis for pathwayidentification to identify Overall design: RNA Seq analysis of apoptotic resistant and WT neutrophils isolated from bone marrow and peritoneum after thiglycollate induced inflammation
Publication Title
Programmed cell removal by calreticulin in tissue homeostasis and cancer.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Mus musculus
- 13 Downloadable Samples
- Affymetrix Murine Genome U74A Version 2 Array (mgu74av2)
Description
The DNA damage response network modulates a wide array of signaling pathways, including DNA repair, cell cycle checkpoints, apoptotic pathways and numerous stress signals. The ATM protein kinase, functionally missing in patients with the human genetic disorder ataxia-telangiectasia (A-T), is a master regulator of this network when the inducing DNA lesions are double strand breaks. The ATM gene is also frequently mutated in sporadic cancers of lymphoid origin. Here, we applied a functional genomics approach that combines gene expression profiling and computational promoter analysis to obtain global dissection of the transcriptional response to ionizing radiation (IR) in murine lymphoid tissue. Cluster analysis revealed six major expression patterns in the data. Prominent among them was a gene cluster that contained dozens of genes whose response to irradiation was Atm-dependent. Computational analysis identified significant enrichment of the binding site signatures of the transcription factors NF-kB and p53 among promoters of these genes, pointing to the major role of these two transcription factors in mediating the Atm-dependent transcriptional response in the irradiated lymphoid tissue. Examination of the response showed that pro- and anti-apoptotic signals were simultaneously induced, with the pro-apoptotic pathway mediated by p53, and the pro-survival pathway by NF-kB. These findings further elucidate the molecular network induced by IR and have implications for cancer management as they suggest that a combined treatment that restores the p53-mediated apoptotic arm while blocking the NF-kB-mediated pro-survival arm could be most successful in increasing the radiosensitivity of lymphoid tumors.
Publication Title
Parallel induction of ATM-dependent pro- and antiapoptotic signals in response to ionizing radiation in murine lymphoid tissue.
Sample Metadata Fields
No sample metadata fields
View Samples