GEO DataSets

(Submitter supplied) Cytokine-activated STAT proteins dimerize and bind to high-affinity motifs, and N-terminal domain-mediated oligomerization of dimers allows tetramer formation and binding to low-affinity tandem motifs, but the functions of dimers versus tetramers are unknown. We generated Stat5a and Stat5b double knock-in (DKI) N-domain mutant mice that form dimers but not tetramers, identified cytokine-regulated genes whose expression required STAT5 tetramers, and defined consensus motifs for dimers versus tetramers. more...

Organism:

Mus musculus

Type:

Expression profiling by array

Platform:

GPL1261

38 Samples

Download data: CEL

(Submitter supplied) This SuperSeries is composed of the SubSeries listed below.

Organism:

Mus musculus

Type:

Expression profiling by array; Expression profiling by high throughput sequencing; Genome binding/occupancy profiling by high throughput sequencing

Platforms:

GPL9250 GPL1261 GPL9185

68 Samples

Download data: BED, CEL, TXT

(Submitter supplied) Cytokine-activated STAT proteins dimerize and bind to high-affinity motifs, and N-terminal domain-mediated oligomerization of dimers allows tetramer formation and binding to low-affinity tandem motifs, but the functions of dimers versus tetramers are unknown. We generated Stat5a and Stat5b double knock-in (DKI) N-domain mutant mice that form dimers but not tetramers, identified cytokine-regulated genes whose expression required STAT5 tetramers, and defined consensus motifs for dimers versus tetramers. more...

Organism:

Mus musculus

Type:

Expression profiling by high throughput sequencing; Genome binding/occupancy profiling by high throughput sequencing

Platforms:

GPL9250 GPL9185

30 Samples

Download data: BED, TXT

(Submitter supplied) Interleukin-15 (IL-15) is essential for the development and maintenance of natural killer (NK) cells. IL-15 activates STAT5 proteins, which can form dimers or tetramers. We previously found that NK cell numbers are decreased in Stat5a-Stat5b tetramer-deficient double knockin (DKI) mice, but the mechanism was not investigated. Here we show that STAT5 dimers are sufficient for NK cell development, whereas STAT5 tetramers mediate NK cell maturation and the expression of maturation-associated genes. more...

Organism:

Mus musculus

Type:

Expression profiling by high throughput sequencing; Genome binding/occupancy profiling by high throughput sequencing

Platform:

GPL13112

19 Samples

Download data: BEDGRAPH, TXT

(Submitter supplied) STAT5 plays a critical role in mediating cellular responses following cytokine stimulation. The activated STAT5 proteins can form dimers and tetramers with distinct biological functions. The role of STAT5 tetramerization in autoimmune-mediated neuroinflammation has not been investigated. Using the STAT5 tetramer-deficient Stat5a-Stat5b N-domain double knock-in (DKI) mouse strain, we report here that STAT5 tetramers promote the pathogenesis of experimental autoimmune encephalomyelitis (EAE). more...

Organism:

Mus musculus

Type:

Expression profiling by high throughput sequencing

Platforms:

GPL13112 GPL18480

13 Samples

Download data: TXT

(Submitter supplied) This SuperSeries is composed of the SubSeries listed below.

Organism:

Mus musculus

Type:

Expression profiling by array; Genome binding/occupancy profiling by high throughput sequencing

Platforms:

GPL6246 GPL14602

21 Samples

Download data: BED, CEL, WIG

(Submitter supplied) CD8 T cells (TCs) expressing active STAT5 (STAT5CA) transcription factors were found to be superior to un-manipulated counterparts in their long-term persistence, capacity to infiltrate a tumor, thrive in its microenvironment and induce its regression. STAT5CA induced sustained expression of genes controlling tissue homing, cytolytic granule composition, Tc-1-associated effector molecules (GranzymeB+/IFNg+/TNFa+/CCL3+ but IL-2-) and potential for secondary responses. more...

Organism:

Mus musculus

Type:

Genome binding/occupancy profiling by high throughput sequencing

Platforms:

GPL15907 GPL14602

3 Samples

Download data: BED, WIG

(Submitter supplied) Transcriptome analyses of naive, effector and memory CD8 TCRP1A lymphocytes expressing or not an active form of the transcription factor Stat5.

Organism:

Mus musculus

Type:

Expression profiling by array

Platform:

GPL6246

19 Samples

Download data: CEL

(Submitter supplied) Recurrent gain-of-function mutations in the transcription factor STAT5B, but not STAT5A, have been detected in mature T- and NK-cell neoplasms. No targeted therapy exists for these heterogeneous and often aggressive diseases. Also, the bystander or balancer role for STAT5A versus STAT5B is unclear. Given this and the shortage of high-fidelity models for peripheral T-cell lymphomas (PTCL), we investigated here whether graded expression of a gain-of-function STAT5A variant produces tumorous T-cell expansions. more...

Organism:

Mus musculus

Type:

Expression profiling by high throughput sequencing

Platform:

GPL17021

15 Samples

Download data: TXT

(Submitter supplied) This SuperSeries is composed of the SubSeries listed below.

Organism:

Mus musculus

Type:

Expression profiling by high throughput sequencing; Methylation profiling by high throughput sequencing

Platforms:

GPL17021 GPL21493

20 Samples

Download data: BED, TXT

(Submitter supplied) The most frequent mutation in STAT5B is the Asp642His (N642H) mutation that was found in >90 leukemic/lymphoma patients. The development of novel treatment against STAT5BN642H has been hindered by the unavailability of a suitable model and the lack of the direct causal effect of STAT5BN642H on T-cell neoplasia development. We herein demonstrate that mice expressing human STAT5BN642H in the hematopoietic compartment rapidly develop leukemia/lymphoma. more...

Organism:

Mus musculus

Type:

Expression profiling by high throughput sequencing

Platform:

GPL17021

14 Samples

Download data: TXT

(Submitter supplied) Cytokines critically control immune responses, but how regulatory programs are altered to allow T cells to differentially respond to distinct cytokine stimuli remains poorly understood. Here, we have globally analyzed enhancer elements bound by IL-2-activated STAT5 and IL-21-activated STAT3 in T cells and identified Il2ra as the top-ranked gene regulated by an IL-2-activated STAT5-bound superenhancer and one of the top genes regulated by STAT3-bound superenhancers. more...

Organism:

Mus musculus

Type:

Expression profiling by high throughput sequencing; Genome binding/occupancy profiling by high throughput sequencing

Platforms:

GPL9250 GPL13112

28 Samples

Download data: BEDGRAPH, TXT

(Submitter supplied) We are interested in unveiling potential gene expression alterations underlying the T cell-related phenotypes observed in DUSP4-/- mice. We used microarray to obtain a macroscopic views of gene profiles comparing freshly isolated splenic T cells from WT and DUSP4-/- mice

Organism:

Mus musculus

Type:

Expression profiling by array

Platform:

GPL16570

6 Samples

Download data: CEL, CHP

(Submitter supplied) The transcription factor STAT5 is fundamental to the mammalian immune system. However, the relationship between its two paralogs, STAT5A and STAT5B, and the extent to which they are functionally distinct, remains controversial. We addressed this longstanding question in primary CD4+ 'helper' T cells, the principal orchestrators of adaptive immunity. Using a combination of genetic and genomic approaches, we demonstrate that, although both influence regulatory (Treg) and effector T cell responses, and control many of the same genes, they are not functionally equivalent and, in fact, only the latter is required for immunological tolerance. more...

Organism:

Mus musculus

Type:

Genome binding/occupancy profiling by high throughput sequencing; Expression profiling by high throughput sequencing

Platforms:

GPL17021 GPL13112

55 Samples

Download data: BW, XLSX

(Submitter supplied) The maintenance of immune homeostasis requires regulatory T cells (Tregs). Given their intrinsic self-reactivity, Tregs must stably maintain a suppressive phenotype to avoid autoimmunity. We report that impaired expression of the transcription factor (TF) Helios by FoxP3+ CD4 and Qa-1-restricted CD8 Tregs results in defective regulatory activity and autoimmunity in mice. Helios-deficient Treg develop an unstable phenotype during inflammatory responses characterized by reduced FoxP3 expression and increased effector cytokine expression secondary to diminished activation of the STAT5 pathway. more...

Organism:

Mus musculus

Type:

Expression profiling by array

Platform:

GPL1261

4 Samples

Download data: CEL

(Submitter supplied) The maintenance of immune homeostasis requires regulatory T cells (Tregs). Given their intrinsic self-reactivity, Tregs must stably maintain a suppressive phenotype to avoid autoimmunity. We report that impaired expression of the transcription factor (TF) Helios by FoxP3+ CD4 and Qa-1-restricted CD8 Tregs results in defective regulatory activity and autoimmunity in mice. Helios-deficient Treg develop an unstable phenotype during inflammatory responses characterized by reduced FoxP3 expression and increased effector cytokine expression secondary to diminished activation of the STAT5 pathway. more...

Organism:

Mus musculus

Type:

Genome binding/occupancy profiling by high throughput sequencing

Platform:

GPL13112

9 Samples

Download data: BW

(Submitter supplied) Natural killer (NK) cells are innate lymphocytes with the capacity to elicit adaptive features, including clonal expansion and immunological memory. Because signal transducer and activator of transcription 5 (STAT5) is essential for NK cell development, the role of this transcription factor and its upstream cytokines IL-2 and IL-15 during infection have not been carefully investigated. In this study, we investigate how STAT5 regulates transcription during viral infection. more...

Organism:

Mus musculus

Type:

Expression profiling by high throughput sequencing

Platform:

GPL21103

12 Samples

Download data: TXT

(Submitter supplied) In response to external stimuli during immune responses, monocytes can have multifaceted roles such as pathogen clearance and tissue repair. However, aberrant control of monocyte activation can result in chronic inflammation and subsequent tissue damage. Granulocyte-macrophage colony-stimulating factor (GM-CSF) induces monocyte differentiation into a heterogenous population of monocyte-derived dendritic cells (moDCs) and macrophages. more...

Organism:

Mus musculus

Type:

Expression profiling by high throughput sequencing

Platform:

GPL13112

18 Samples

Download data: TXT

(Submitter supplied) STAT5 is critical for inducing lineage specifying transcription factors, establishing effector gene programs, upregulating IL-2Rα (also known as CD25), and supporting cell survival in response to environmental cues in mature T cells. Although it has been shown that IL-7-induced STAT5 signaling is also essential for survival of thymic precursor cells, the exact roles of STAT5A and STAT5B and their target genes that contribute to the developmental program in early thymic development have been unknown. more...

Organism:

Mus musculus

Type:

Expression profiling by high throughput sequencing

Platform:

GPL17021

8 Samples

Download data: TXT

(Submitter supplied) Interleukin (IL)-2 and IL-21 dichotomously shape CD8+ T cell differentiation. IL-2 drives terminal differentiation, generating cells that are poorly effective against tumors, whereas IL-21 promotes stem cell memory T cells (TSCM) and antitumor responses. Here we investigated the role of metabolic programming in the developmental differences induced by these cytokines. IL-2 promoted effector-like metabolism and aerobic glycolysis, robustly inducing lactate dehydrogenase (LDH) and lactate production, whereas IL-21 maintained a metabolically quiescent state dependent on oxidative phosphorylation. more...

Organism:

Mus musculus

Type:

Expression profiling by high throughput sequencing

Platform:

GPL21493

10 Samples

Download data: TXT