Mus musculus
Ontology highlight
ABSTRACT:
OTHER RELATED OMICS DATASETS IN: E-GEOD-36888
PROVIDER: PRJNA157371 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:This SuperSeries is composed of the following subset Series: GSE36882: Critical Role of STAT5 Transcription Factor Tetramerization for Cytokine Responses and Normal Immune Function (ChIP-Seq and RNA-Seq) GSE36888: Critical Role of STAT5 Transcription Factor Tetramerization for Cytokine Responses and Normal Immune Function (RNA) Refer to individual Series
2012-04-24 | E-GEOD-36890 | biostudies-arrayexpress
Project description:Critical Role of STAT5 Transcription Factor Tetramerization for Cytokine Responses and Normal Immune Function
| PRJNA157327 | ENA
Project description:Critical Role of STAT5 Transcription Factor Tetramerization for Cytokine Responses and Normal Immune Function (ChIP-Seq and RNA-Seq)
| PRJNA157369 | ENA
Project description: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. Whereas Stat5- deficient mice exhibited perinatal lethality, DKI mice were viable, indicating that STAT5 dimers were sufficient for survival. Nevertheless, STAT5 DKI mice had fewer CD4+CD25+ T cells, NK cells, and CD8+ T cells, with impaired cytokine-induced proliferation and homeostatic proliferation of CD8+ T cells. DKI CD8+ T cell proliferation following viral infection was diminished and DKI Treg cells did not efficiently control colitis. Thus, tetramerization of STAT5 is dispensable for survival but is critical for cytokine responses and normal immune function. T cells were extracted from spleen of wt and STAT5 double knocked in mice, and treated with IL-2. The cells were collected from 0h (without treatment), 2h, 6h and 17h, and chipped on Affy mouse 430 2.0 arrays.
2012-04-24 | E-GEOD-36888 | biostudies-arrayexpress
Project description: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. Whereas Stat5- deficient mice exhibited perinatal lethality, DKI mice were viable, indicating that STAT5 dimers were sufficient for survival. Nevertheless, STAT5 DKI mice had fewer CD4+CD25+ T cells, NK cells, and CD8+ T cells, with impaired cytokine-induced proliferation and homeostatic proliferation of CD8+ T cells. DKI CD8+ T cell proliferation following viral infection was diminished and DKI Treg cells did not efficiently control colitis. Thus, tetramerization of STAT5 is dispensable for survival but is critical for cytokine responses and normal immune function. Genome-wide mapping of STAT5A,STAT5B binding in mouse WT and DKI T cells (cultured with or without IL-2 for 1 hr) was conducted. RNA-Seq is conducted in mouse CD8+ T cells (WT and DKI, non-treated or treated with IL-2/IL-15 for 4 hr, 24 hr, 48 hr and 72 hr)
2012-04-25 | E-GEOD-36882 | biostudies-arrayexpress
Project description: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. Whereas Stat5- deficient mice exhibited perinatal lethality, DKI mice were viable, indicating that STAT5 dimers were sufficient for survival. Nevertheless, STAT5 DKI mice had fewer CD4+CD25+ T cells, NK cells, and CD8+ T cells, with impaired cytokine-induced proliferation and homeostatic proliferation of CD8+ T cells. DKI CD8+ T cell proliferation following viral infection was diminished and DKI Treg cells did not efficiently control colitis. Thus, tetramerization of STAT5 is dispensable for survival but is critical for cytokine responses and normal immune function.
2012-04-26 | GSE36882 | GEO
Project description: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. Whereas Stat5- deficient mice exhibited perinatal lethality, DKI mice were viable, indicating that STAT5 dimers were sufficient for survival. Nevertheless, STAT5 DKI mice had fewer CD4+CD25+ T cells, NK cells, and CD8+ T cells, with impaired cytokine-induced proliferation and homeostatic proliferation of CD8+ T cells. DKI CD8+ T cell proliferation following viral infection was diminished and DKI Treg cells did not efficiently control colitis. Thus, tetramerization of STAT5 is dispensable for survival but is critical for cytokine responses and normal immune function.
2012-04-25 | GSE36888 | GEO
Project description: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. CD8 Treg also require Helios-dependent STAT5 activation for survival and to prevent terminal T cell differentiation. Definition of Helios as a key transcription factor that stabilizes regulatory T-cells in the face of inflammatory responses provides a genetic explanation for a core property of regulatory T-cells. We used microarrays to detail the global programs of gene expression by CD8 Treg (CD44+CD122+Ly49+) and conventional memory type of CD8 cells (CD44+CD122+Ly49-).
2015-09-15 | E-GEOD-73015 | biostudies-arrayexpress
Project description:In breast cancer, interactions between tumor cells and surrounding stromal cells, such as macrophages, are critical for tumor growth, progression, and therapeutic response. Recent studies have highlighted the complex nature and heterogeneous populations of macrophages associated with both tumor promoting and tumor inhibiting phenotypes. Identifying the specific signaling pathways that regulate macrophage function within the tumor microenvironment will lead to new approaches that suppress tumor promoting functions while enhancing their anti-tumor functions. We demonstrated STAT5 (signal transducer and activator of transcription 5) is robustly activated in tumor-associated macrophages and that granulocyte-macrophage colony stimulating factor (GM-CSF) is a major cytokine stimulating this pathway. To define impacts of GM-CSF/STAT5 on macrophage function, we used in vitro and in vivo models to demonstrate that STAT5 has a significant role in stimulating expression profiles in macrophages consistent with an anti-tumor, adaptive immune response. Our results also indicate that loss of STAT5 in the myeloid lineage leads to enhanced metastatic disease. These findings reveal that disrupted STAT5 signaling in tumor-associated macrophages supports tumor progression, which suggests STAT5 may regulate anti-tumor macrophage function. Understanding how to enhance the anti-tumor capacity of macrophages will be vital in developing effective treatment strategies for patients with aggressive breast cancer.
2021-11-17 | GSE171428 | GEO
Project description:Innate lymphoid cells (ILCs) patrol environmental interfaces to defend against infection and protect barrier integrity. Using a genetic tuning model, we demonstrate that the signal-dependent transcription factor STAT5 is critical for accumulation of all known ILC subsets in mice, and reveal a hierarchy of STAT5 dependency for populating lymphoid and non-lymphoid tissues. We also apply transcriptome and genomic distribution analyses to define a STAT5 gene signature in NK cells, the prototypical ILC subset, and provide a systems-based molecular rationale for its key functions downstream of IL-15. Additionally, we uncover surprising features of STAT5 behavior, most notably, the wholesale re-distribution that occurs when NK cells shift from tonic signaling to acute cytokine-driven signaling, and its genome-wide coordination with T-bet, another key transcription factor in ILC biology. Collectively, our data position STAT5 as a central node in the transcription factor network that instructs ILC development, homeostasis and function, and provide mechanistic insights on how it works at cellular and molecular levels.
2017-09-13 | GSE100674 | GEO