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GSE26551
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.
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, Homo sapiens
- 8 Downloadable Samples
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Continuous expression of the transcription factor e2-2 maintains the cell fate of mature plasmacytoid dendritic cells.
Sample Metadata Fields
Specimen part, Cell line, Time
View Samples- Mus musculus
- 24 Downloadable Samples
Description
High-density lipoproteins (HDLs) protect pancreatic cells against apoptosis. This property might be related to the increased risk to develop diabetes in patients with low HDL blood levels. However, the mechanisms by which HDLs protect cells are poorly characterized. Here we use a transcriptomic approach to identify genes differentially modulated by HDLs in cells subjected to apoptotic stimuli.
Publication Title
Involvement of 4E-BP1 in the protection induced by HDLs on pancreatic beta-cells.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Mus musculus
- 48 Downloadable Samples
Description
The regulatory logic underlying global transcriptional programs controlling development of visceral organs like the pancreas remains undiscovered. Here, we profiled gene expression in 12 purified populations of fetal and adult pancreatic epithelial cells representing crucial progenitor cell subsets, and their endocrine or exocrine progeny. Using probabilistic models to decode the general programs organizing gene expression, we identified co-expressed gene modules in cell subsets that revealed patterns and processes governing progenitor cell development, lineage specification, and endocrine cell maturation. Module network analysis linked established regulators like Neurog3 to unrecognized roles in endocrine secretion and protein transport, and nominated multiple candidate regulators of pancreas development. Phenotyping mutant mice revealed that candidate regulatory genes encoding transcription factors, including Bcl11a, Etv1, Prdm16 and Runx1t1, are essential for pancreas development or glucose control. Our integrated approach provides a unique framework for identifying regulatory networks underlying pancreas development and diseases like diabetes mellitus.
Publication Title
An integrated cell purification and genomics strategy reveals multiple regulators of pancreas development.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 4 Downloadable Samples
Description
Immortalized, amelanotic melanocytes isolted from skin of Balb/c express enzymatically-inactive tyrosinase due to a homozygous point mutation (TGT->TCT) in tyrosinase gene, resulting in a lack of melanin . To serve as a control cell line, pigmentation was restored in these cells by correcting the point mutation using an RNA-DNA oligonucleotide (kingly gift from Dr. Alexeev Y. Vitali).
Publication Title
Melanocyte-secreted fibromodulin promotes an angiogenic microenvironment.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus, Homo sapiens
- 12 Downloadable Samples
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Enhancer variants reveal a conserved transcription factor network governed by PU.1 during osteoclast differentiation.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus, Homo sapiens
- 8 Downloadable Samples
Description
Similar temporal expression kinetics of transcription factors in human and mouse osteoclast differentiation evaluated by microarray
Publication Title
Enhancer variants reveal a conserved transcription factor network governed by PU.1 during osteoclast differentiation.
Sample Metadata Fields
Specimen part
View Samples