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GSE26069
Mus musculus
8 Downloadable Samples
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Evolutionary etiology of high-grade astrocytomas.
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Sex, Time
View Samples- Mus musculus
- 8 Downloadable Samples
Description
To determine the regulatory pathways necessary for astrocytoma formation within complex adult brain microenvironments, we engineered mice for adult astrocyte-specific disruption of key regulators (pRb, Kras and Pten). Drivers of all astrocytoma grades were identified using CreERTM-inducible alleles. Inactivation of pRb was necessary to initiate grade II disease, and was the only lesion to do so. Additional activation of Kras progressed disease to grade III, while further Pten inactivation facilitated grade IV (glioblastoma) progression. These outcomes were elicited whether somatic events were induced broadly or focally. In vivo inactivation of pRb, which induced astrocyte proliferation and apoptosis, activated the MAPK pathway, while Kras activation and Pten loss triggered PI3K pathways.
Publication Title
Evolutionary etiology of high-grade astrocytomas.
Alternate Accession IDs
Sample Metadata Fields
Sex, Time
View Samples- Mus musculus
- 16 Downloadable Samples
Description
STAT3, an essential transcription factor with pleiotropic functions, plays critical roles in the pathogenesis of autoimmunity. Despite recent data linking STAT3 with inflammatory bowel disease, exactly how it contributes to chronic intestinal inflammation is not known. Using a T cell transfer model of colitis we found that STAT3 expression in T cells was essential for the induction of both colitis and systemic inflammation. STAT3 was critical in modulating the balance of T helper 17 (Th17) and regulatory T (Treg) cells, as well as in promoting CD4+ T cell proliferation. We used chromatin immunoprecipitation and massive parallel sequencing (ChIP-Seq) to define the genome-wide targets of STAT3 in CD4+ T cells. We found that STAT3 bound to multiple genes involved in Th17 cell differentiation, cell activation, proliferation and survival, regulating both expression and epigenetic modifications. Thus, STAT3 orchestrates multiple critical aspects of T cell function in inflammation and homeostasis.
Publication Title
Diverse targets of the transcription factor STAT3 contribute to T cell pathogenicity and homeostasis.
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Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 16 Downloadable Samples
Description
STAT3, an essential transcription factor with pleiotropic functions, plays critical roles in the pathogenesis of autoimmunity. Despite recent data linking STAT3 with inflammatory bowel disease, exactly how it contributes to chronic intestinal inflammation is not known. Using a T cell transfer model of colitis we found that STAT3 expression in T cells was essential for the induction of both colitis and systemic inflammation. STAT3 was critical in modulating the balance of T helper 17 (Th17) and regulatory T (Treg) cells, as well as in promoting CD4+ T cell proliferation. We used chromatin immunoprecipitation and massive parallel sequencing (ChIP-Seq) to define the genome-wide targets of STAT3 in CD4+ T cells. We found that STAT3 bound to multiple genes involved in Th17 cell differentiation, cell activation, proliferation and survival, regulating both expression and epigenetic modifications. Thus, STAT3 orchestrates multiple critical aspects of T cell function in inflammation and homeostasis.
Publication Title
Diverse targets of the transcription factor STAT3 contribute to T cell pathogenicity and homeostasis.
Alternate Accession IDs
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 4 Downloadable Samples
Description
Interleukin 2 (IL-2), a cytokine linked to human autoimmune diseases, limits IL-17 production. We show that deletion of Stat3 in T cells abrogates IL-17 production and attenuates autoimmunity associated with IL-2 deficiency. While STAT3 induces IL-17 and RORt and inhibits Foxp3, IL-2 inhibited IL-17 independently of Foxp3 and RORt. We found that STAT3 and STAT5 bound to multiple common sites across the Il17 genetic locus. The induction of STAT5 binding by IL-2 was associated with a reduction in STAT3 binding at these sites and the inhibition of associated active epigenetic marks. Titrating the relative activation of STAT3 and STAT5 modulated TH17 cell specification. Thus, the balance rather than the absolute magnitude of these signals determines the propensity of cells to make a key inflammatory cytokine.
Publication Title
Opposing regulation of the locus encoding IL-17 through direct, reciprocal actions of STAT3 and STAT5.
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Specimen part
View Samples- Mus musculus
- 1 Downloadable Sample
Description
We compare the transcriptome of two different clones of multipotent adult progenitor cells (MAPCs) using Affymetrix arrays.
Publication Title
Hematopoietic reconstitution by multipotent adult progenitor cells: precursors to long-term hematopoietic stem cells.
Alternate Accession IDs
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No sample metadata fields
View Samples- Mus musculus
- 10 Downloadable Samples
Description
CD4+ T cells that selectively produce interleukin (IL)-17, are critical for host defense and autoimmunity1-4. Crucial for T helper17 (Th17) cells in vivo5,6, IL-23 has been thought to be incapable of driving initial differentiation. Rather, IL-6 and transforming growth factor (TGF)-1 have been argued to be the factors responsible for initiating specification7-10. Herein, we show that Th17 differentiation occurs in the absence of TGF- signaling. Neither IL-6 nor IL-23 alone efficiently generated Th17 cells; however, these cytokines in combination with IL-1 effectively induced IL-17 production in nave precursors, independently of TGF-. Epigenetic modification of the Il17a/Il17f and Rorc promoters proceeded without TGF-1, allowing the generation of cells that co-expressed Rort and T-bet. T-bet+Rort+ Th17 cells are generated in vivo during experimental allergic encephalomyelitis (EAE), and adoptively transferred Th17 cells generated with IL-23 in the absence of TGF-1 were more pathogenic in this experimental disease. These data suggest a new model for Th17 differentiation. Consistent with genetic data linking the IL23R with autoimmunity, our findings re-emphasize the role of IL-23 and therefore have important implications for the development of new therapies.
Publication Title
Generation of pathogenic T(H)17 cells in the absence of TGF-β signalling.
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Treatment
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