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GSE11818
Mus musculus
6 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
A new Treg-specific, FoxP3-GFP-hCre BAC transgenic was crossed to a conditional Dicer knock-out mouse strain to analyze the role of microRNAs (miRNA) in the development and function of regulatory T cells (Tregs). Although thymic Tregs developed normally in this setting, the cells showed evidence of altered differentiation and dysfunction in the periphery. Dicer-deficient Treg lineage cells failed to remain stable as a subset of cells down-regulated the Treg-specific transcription factor, FoxP3, while the majority expressed altered levels of multiple genes and proteins (including Neuropilin 1, GITR and CTLA-4) associated with the Treg fingerprint. In fact, a significant percentage of the Treg lineage cells took on a Th memory phenotype including increased levels of CD127, IL-4, and interferon-g. Importantly, Dicer-deficient Tregs lost suppression activity in vivo; the mice rapidly developed fatal systemic autoimmune disease resembling the FoxP3 knockout phenotype. These results support a central role for miRNAs in maintaining the stability of differentiated Treg function in vivo and homeostasis of the adaptive immune system.
Publication Title
Selective miRNA disruption in T reg cells leads to uncontrolled autoimmunity.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 4 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Foxp3 is indispensable for Treg suppressive function, but the stability of Foxp3 has been controversial. In autoimmune arthritis, Th17 cells play a critically important pathological role, but the origin of Th17 cells remains unknown
Publication Title
Pathogenic conversion of Foxp3+ T cells into TH17 cells in autoimmune arthritis.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus, Homo sapiens
- 36 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
CD28-inducible transcription factor DEC1 is required for efficient autoreactive CD4+ T cell response.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Mus musculus
- 24 Downloadable Samples
Illumina HiSeq 2500
Description
Regulatory T cells (Tregs) are essential for maintaining proper immune homeostasis. Extracellular signals (e.g. TCR, CD28, IL-2R) are necessary for the generation and maintenance of Tregs, but how these signals are integrated to control the gene expression patterns of Tregs is less clear. Here we show that the epigenetic regulator, Ezh2, was induced by CD28 costimulation and Ezh2 activity was elevated in Tregs as compared to conventional CD4+ T cells. Deletion of Ezh2 in mouse Tregs led to a progressive autoimmune disease because Tregs were compromised after activation, losing proper control of essential Treg lineage genes and adopting a gene expression pattern similar to Foxp3-deficient ‘Tregs.’ Lineage-tracing of Ezh2-deficient Tregs in vivo confirmed that the cells were destabilized selectively in activated Treg populations, which led to a significant loss of Tregs in non-lymphoid tissues. These studies reveal an essential role for Ezh2 in the maintenance of Treg “identity” during cellular activation and differentiation. Overall design: RNAseq of sorted populations of CD62Lhi or CD62Llo Tregs for both Ezh2-HET (Foxp3YFP-Cre/Foxp3WT;Ezh2fl/+ female mice) and Ezh2-KO (Foxp3YFP-Cre/Foxp3WT;Ezh2fl/fl female mice) were generated, in triplicate for each condition, using Illumina HiSeq 2500 single-end 50bp sequencing platform.
Publication Title
The chromatin-modifying enzyme Ezh2 is critical for the maintenance of regulatory T cell identity after activation.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 21 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
We used microarrays to detail the global gene transcription underlying T cells activation during the first 24 hours after stimulation.
Publication Title
CD28-inducible transcription factor DEC1 is required for efficient autoreactive CD4+ T cell response.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Mus musculus
- 15 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
We used microarrays to detail the global gene transcription effect of Dec1 underlying T cells activation during the first 24 hours after stimulation.
Publication Title
CD28-inducible transcription factor DEC1 is required for efficient autoreactive CD4+ T cell response.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Homo sapiens
- 39 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Microarray used to detail the global gene transcription underlying sorted IFNg+ and IFNg- Tregs (CD4+CD25+CD127lo) and Tconv (CD4+CD25-CD127+) for fresh (unexpanded) and 14 day expanded cells from human blood.
Publication Title
Divergent Phenotypes of Human Regulatory T Cells Expressing the Receptors TIGIT and CD226.
Sample Metadata Fields
Specimen part, Disease stage, Treatment, Subject
View Samples- Homo sapiens
- 22 Downloadable Samples
- Sentrix Human-6 Expression BeadChip
Description
Regulatory T (Treg) cells are involved in self tolerance, immune homeostasis, prevention of autoimmunity, and suppression of immunity to pathogens or tumours. The forkhead transcription factor FOXP3 is essential for Treg cell development and function as mutations in FOXP3 cause severe autoimmunity in mice and humans. However, the FOXP3-dependent molecular mechanisms leading to this severe phenotype are not well understood. Here we introduce the chromatin remodelling enzyme SATB1 (special AT-rich sequence-binding protein-1) as an important target gene of FOXP3. So far, SATB1 has been associated with normal thymic T-cell development, peripheral T-cell homeostasis, TH1/TH2 polarization, and reprogramming of gene expression. In natural and induced murine and human FOXP3+ Treg cells SATB1 expression is significantly reduced. While there is no differential epigenetic regulation of the SATB1 locus between Treg and Teffector cells, FOXP3 reduces SATB1 expression directly as a transcriptional repressor at the SATB1 locus and indirectly via miR-155 induction, which specifically binds to the 3UTR of the SATB1 mRNA. Reduced SATB1 expression in FOXP3+ cells achieved either by overexpression or induction of FOXP3 is linked to significant reduction in TH1 and TH2 cytokines, while loss of FOXP3 function either by knock down or genetic mutation leads to significant upregulation of SATB1 and subsequent cytokine production. Alltogether, these findings demonstrate that reduced SATB1 expression in Treg cells is necessary for maintenance of a Treg-cell phenotype in vitro and in vivo and places SATB1-mediated T cell-specific modulation of global chromatin remodelling central during the decision process between effector and regulatory T-cell function.
Publication Title
Repression of the genome organizer SATB1 in regulatory T cells is required for suppressive function and inhibition of effector differentiation.
Sample Metadata Fields
Specimen part, Disease, Disease stage, Treatment
View Samples- Mus musculus
- 22 Downloadable Samples
- NextSeq 500
Description
We transduced clonally MLL-AF9 leukemia cells expressing cas9 with sgRNA targeting the jumonji and zinc finger domains of JMJD1C. GFP (MLL-AF9) and TdTomato (sgRNA) double positive cells were sorted on Day 6 after transduction. Total RNA was isolated followed by mRNA selection. cDNA libraries were generated and NextGen Sequencing was performed. Overall design: We performed RNA-seq in mouse MLL-AF9 cas9 cells harboring sgRNA against jumonji and zinc finger domains of JMJD1C or renilla.
Publication Title
Critical role of Jumonji domain of JMJD1C in MLL-rearranged leukemia.
Sample Metadata Fields
Specimen part, Subject
View Samples- Mus musculus
- 8 Downloadable Samples
- NextSeq 500
Description
We performed single-cell sequencing on mouse MLL-AF9-cas9 leukemia cells 7 days after transduction with sgRNA against Renilla or JMJD1C JmjC domain. We revealed heterogeneity within each population. Overall design: We performed single-cell sequencing on mouse MLL-AF9 cells harboring JMJD1C sgRNA targeting jumonji domain or renilla control sgRNA.
Publication Title
Critical role of Jumonji domain of JMJD1C in MLL-rearranged leukemia.
Sample Metadata Fields
Specimen part, Subject
View Samples