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GSE26600
Mus musculus
91 Downloadable Samples
Description
Methylazoxymethanol (MAM), the genotoxic metabolite of the cycad azoxyglucoside cycasin, induces genetic alterations in bacteria, yeast, plants, insects and mammalian cells, but adult nerve cells are thought to be unaffected. We show that the brains of young adult mice treated with a single systemic dose of MAM display DNA damage (O6-methylguanine lesions) that peaks at 48 hours and decline to near-normal levels at 7 days post-treatment. By contrast, at this time, MAM-treated mice lacking the gene encoding the DNA repair enzyme O6-methylguanine DNA methyltransferase (MGMT), showed persistent O6-methylguanine DNA damage. The DNA damage was linked to cell-signaling pathways that are perturbed in cancer and neurodegenerative disease. These data are consistent with the established carcinogenic and developmental neurotoxic properties of MAM in rodents, and they support the proposal that cancer and neurodegeneration share common signal transduction pathways. They also strengthen the hypothesis that early life exposure to the MAM glucoside cycasin has an etiological association with a declining, prototypical neurodegenerative disease seen in Guam, Japan, and New Guinea populations that formerly used the neurotoxic cycad plant for medicine and/or food. Exposure to environmental genotoxins may have relevance to the etiology of related tauopathies, notably, Alzheimers disease, as well as cancer.
Publication Title
The cycad genotoxin MAM modulates brain cellular pathways involved in neurodegenerative disease and cancer in a DNA damage-linked manner.
Sample Metadata Fields
Sex, Specimen part, 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.
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.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 12 Downloadable Samples
Description
Neutrophil abscess formation is critical in innate immunity against many pathogens. Here, the mechanism of neutrophil abscess formation was investigated using a mouse model of Staphylococcus aureus cutaneous infection. Gene expression analysis of S. aureus-infected skin revealed that induction of neutrophil recruitment genes was largely dependent upon IL-1beta/IL-1R activation. Unexpectedly, using IL 1beta reporter mice, neutrophils were identified as the primary source of IL-1beta at the site of infection. Furthermore, IL-1beta-producing neutrophils were necessary and sufficient for abscess formation and bacterial clearance. S. aureus-induced IL 1beta production by neutrophils required TLR2, NOD2, FPRs and the ASC/NLRP3 inflammasome. Taken together, IL-1beta and neutrophil abscess formation during an infection are functionally, spatially and temporally linked as a consequence of direct IL-1beta production by neutrophils.
Publication Title
Neutrophil-derived IL-1β is sufficient for abscess formation in immunity against Staphylococcus aureus in mice.
Sample Metadata Fields
Specimen part
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.
Sample Metadata Fields
Treatment
View Samples- Mus musculus
- 24 Downloadable Samples
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Reversal of Alopecia Areata Following Treatment With the JAK1/2 Inhibitor Baricitinib.
Sample Metadata Fields
Specimen part, Treatment, Time
View Samples- Mus musculus
- 12 Downloadable Samples
Description
The C3H/HeJ grafted model of alopecia areata was used to determine the efficacy of systemic baricitinib at preventing alopecia or treating established disease.
Publication Title
Reversal of Alopecia Areata Following Treatment With the JAK1/2 Inhibitor Baricitinib.
Sample Metadata Fields
Specimen part, Treatment, Time
View Samples- Mus musculus
- 12 Downloadable Samples
Description
The C3H/HeJ grafted model of alopecia areata was used to determine the efficacy of systemic baricitinib at preventing alopecia or treating established disease.
Publication Title
Reversal of Alopecia Areata Following Treatment With the JAK1/2 Inhibitor Baricitinib.
Sample Metadata Fields
Specimen part, Treatment, Time
View Samples- Mus musculus
- 6 Downloadable Samples
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Sequentially acting Sox transcription factors in neural lineage development.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 6 Downloadable Samples
Description
We report sequential binding but unique functions of different Sox transcription factors during distinct stages of neural differentiation
Publication Title
Sequentially acting Sox transcription factors in neural lineage development.
Sample Metadata Fields
Specimen part
View Samples