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SRP008477
Mus musculus
2 Downloadable Samples
Illumina Genome Analyzer
Description
Natural killer (NK) cells play a critical role in early host defense to infected and transformed cells. Here we show that mice deficient in Eri1, a conserved 3’-to-5’ exoribonuclease that represses RNA interference, have a cell-intrinsic defect in NK cell development and maturation. Eri1–/– NK cells displayed delayed acquisition of Ly49 receptors in the bone marrow and a selective reduction in Ly49D and Ly49H activating receptors in the periphery. Eri1 was required for immune-mediated control of mouse cytomegalovirus (MCMV) infection. Ly49H+ NK cells deficient in Eri1 failed to expand efficiently during MCMV infection, and virus-specific responses were also diminished among Eri1–/– T cells. We identified miRNAs as the major endogenous small RNA target of Eri1 in mouse lymphocytes. Both NK and T cells deficient in Eri1 displayed a global, sequence-independent increase in miRNA abundance. Ectopic Eri1 expression rescued defective miRNA expression in mature Eri1–/– T cells. Thus, mouse Eri1 regulates miRNA homeostasis in lymphocytes and is required for normal NK cell development and anti-viral immunity. Overall design: Small RNA profiling from wildtype and Eri1-deficient mouse CD4+ T cells
Publication Title
Eri1 regulates microRNA homeostasis and mouse lymphocyte development and antiviral function.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Mus musculus
- 115 Downloadable Samples
- Illumina HiSeq 2000, Illumina HiSeq 1500
Description
Roquin proteins are required to preclude spontaneous T cell activation and aberrant T follicular helper (Tfh) or T helper 17 (Th17) differentiation. Here, we show that deletion of Roquin encoding alleles in regulatory T cells (Tregs) also caused the activation of conventional T cells. These Tregs exhibited a follicular Treg phenotype, CD25 downregulation and could not protect from colitis. Mechanistically, Roquin was required for full expression and activity of Pten and Foxo1, two essential signaling molecules in Tregs and effector T cells. Roquin upregulated Pten by interfering with miR-17~92 binding to an overlapping cis-element in the Pten 3' UTR and downregulated the Foxo1-specific E3 ubiquitin ligase Itch. Loss of Roquin enhanced mTOR signaling and global protein synthesis, while inhibition of PI3K or mTOR in Roquin-deficient CD4+ T cells corrected increased Tfh and Th17 differentiation. Thereby, the control of PI3K-mTOR signaling by Roquin prevents autoimmunity through T cell-intrinsic and Treg-mediated regulation. Overall design: Examination of transcriptome and ribosome occupancy in MEF and T cells upon Roquin expression and inhibition. Examination of Roquin binding sites in the mouse transcriptome of MEF cells. Examination of transcriptome in CD25+ and CD25- Treg cells from WT and Roquin DKO mice.
Publication Title
Roquin targets mRNAs in a 3'-UTR-specific manner by different modes of regulation.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Mus musculus
- 7 Downloadable Samples
Affymetrix Mouse Gene 2.0 ST Array (mogene20st)
Description
Fibrosis is a leading cause of deaths in industrialized countries and has no effective therapy. We demonstrated that blockade of OX40L prevented inflammation-driven fibrosis affecting the skin and the lungs and promotes regression of established dermal fibrosis in different murine models.
Publication Title
OX40L blockade protects against inflammation-driven fibrosis.
Sample Metadata Fields
Sex, Age, Specimen part, Treatment
View Samples- Mus musculus
- 4 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Mechanisms of epigenetic and cell-type specific regulation of Hey target genes in ES cells and cardiomyocytes.
Sample Metadata Fields
Specimen part
View Samples- Danio rerio
- 9 Downloadable Samples
- Affymetrix Zebrafish Genome Array (zebrafish)
Description
In gastrulation, distinct progenitor cell populations are induced and sorted into the three germ layers ectoderm, mesoderm and endoderm. In order to identify genes involved in germ layer specification and morphogenesis, we identified genes differentially expressed between ectodermal and mesendodermal progenitor cells. To do so, we first generated highly enriched pools of ectodermal and mesendodermal progenitor cells. Mesendodermal cells were generated by over-expressing the Nodal signal Cyclops in wild type embryos and ectodermal cells were taken from mz-one-eyed-pinhead (oep) mutant embryos. We then compared the transcriptome of ectodermal versus mesendodermal cells taken from embryos at 7 hours post fertilization (hpf). In wild type embryos at this stage (70% epiboly), the first ectodermal and mesendodermal progenitor cells have already been sorted into their respective germ layers and ingression of mesendodermal progenitors is still ongoing.
Publication Title
Identification of regulators of germ layer morphogenesis using proteomics in zebrafish.
Sample Metadata Fields
Age, Specimen part, Subject, Time
View Samples- Mus musculus
- 4 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
We used an in vitro cardiomyocyte differentiation system with inducible Hey1 or Hey2 expression to study target gene regulation in cardiomyocytes (CM) generated from murine embryonic stem cells (ESC). The effects of Hey1 and Hey2 are largely redundant, but cell type specific. The number of regulated genes is comparable between ESC and CM, but the total number of binding sites is much higher, especially in ESC, targeting mainly genes involved in transcriptional regulation and developmental processes. Repression by Hey generally correlates with the extent of Hey-binding to target promoters, subsequent Hdac recruitment and lower histone acetylation. Functionally, treatment with the Hdac inhibitor TSA abolished Hey target gene regulation. However, in CM the repressive effect of Hey-binding is lost for a subset of genes. These lack Hey-dependent histone deacetylation in CM and are enriched for binding sites of cardiac specific activators like Srf, Nkx2-5, and Gata4.
Publication Title
Mechanisms of epigenetic and cell-type specific regulation of Hey target genes in ES cells and cardiomyocytes.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 4 Downloadable Samples
Description
We used an in vitro cardiomyocyte differentiation system with inducible Hey1 or Hey2 expression to study target gene regulation in cardiomyocytes (CM) generated from murine embryonic stem cells (ESC). The effects of Hey1 and Hey2 are largely redundant, but cell type specific. The number of regulated genes is comparable between ESC and CM, but the total number of binding sites is much higher, especially in ESC, targeting mainly genes involved in transcriptional regulation and developmental processes. Repression by Hey generally correlates with the extent of Hey-binding to target promoters, subsequent Hdac recruitment and lower histone acetylation. Functionally, treatment with the Hdac inhibitor TSA abolished Hey target gene regulation. However, in CM the repressive effect of Hey-binding is lost for a subset of genes. These lack Hey-dependent histone deacetylation in CM and are enriched for binding sites of cardiac specific activators like Srf, Nkx2-5, and Gata4. Overall design: ES cells and cardiomyocytes with Hey1 or Hey2 overexpression were compared to control cells
Publication Title
Mechanisms of epigenetic and cell-type specific regulation of Hey target genes in ES cells and cardiomyocytes.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 10 Downloadable Samples
- Illumina HiSeq 2500
Description
RNA-seq analysis of murine eGFP+ relbfl/flnfkb2fl/flCg1-Cre and Cg1-Cre splenic germinal center B cells identifies genes regulated by the transcription factors RELB and p52 (NF-kB2) in germinal center B cells. Overall design: Germinal center B cells from 12-week old relbfl/flnfkb2fl/flCg1-Cre and Cg1-Cre littermate mice immunized with sheep red blood cells (SRBC) were isolated at day 7 after immunization by flow cytometric sorting from splenic mononuclear cells. RNA was isolated, amplified and submitted for RNA-sequencing on an Illumina HiSeq2500 instrument for 35-40 million 2x50 paired-ended reads.
Publication Title
Transcription factors of the alternative NF-κB pathway are required for germinal center B-cell development.
Sample Metadata Fields
Age, Specimen part, Subject
View Samples- Mus musculus
- 8 Downloadable Samples
- Affymetrix Mouse Gene 2.0 ST Array (mogene20st)
Description
Interleukin-1 receptor associated kinase 1 (IRAK1) is an important component of the IL-1R and TLR signaling pathways, which influence Th cell differentiation. Here, we show that IRAK1 promotes Th17 development by mediating IL-1 induced upregulation of IL-23R and subsequent STAT3 phosphorylation, thus enabling sustained IL-17 production. Moreover, we show that IRAK1 signaling fosters Th1 differentiation by mediating T-bet induction and counteracts Treg generation. Cotransfer experiments revealed that Irak1-deficient CD4+ T cells have a cell-intrinsic defect in generating Th1 and Th17 cells under inflammatory conditions in spleen, mesenteric lymph nodes and colon tissue. Furthermore, IRAK1 expression in T cells was shown to be essential for T cell accumulation in the inflamed intestine and mLNs. Transcriptome analysis ex vivo revealed that IRAK1 promotes T cell activation and induction of gut-homing molecules in a cell-intrinsic manner. Accordingly, Irak1-deficient T cells failed to upregulate surface expression of 47 integrin after transfer into Rag1-/- mice and their ability to induce colitis was greatly impaired. Lack of IRAK1 in recipient mice provided additional protection from colitis. Therefore, IRAK1 plays an important role in intestinal inflammation by mediating T cell activation, differentiation and their accumulation in the gut. Thus, IRAK1 is a promising novel target for therapy of inflammatory bowel diseases.
Publication Title
IRAK1 Drives Intestinal Inflammation by Promoting the Generation of Effector Th Cells with Optimal Gut-Homing Capacity.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 6 Downloadable Samples
- Illumina HiSeq 2000
Description
RNAseq analysis of CD40 + IgM in vitro-stimulated (6 hours) murine relafl/flCD19-Cre (furtheron designated as RELA) and CD19-Cre (furtheron designated as WT) splenic B cells identifies genes regulated by the transcription factor RELA in activated B cells. Overall design: Splenic B cells from 12-week old relafl/flCD19-Cre and CD19-Cre littermate mice were isolated by magnetic cell separation from splenic mononuclear cells and stimulated in vitro for 6 hours with anti-CD40 and anti-IgM. RNA was isolated and submitted for RNA-sequencing on an Illumina HiSeq2000 instrument for 30 million single-ended reads.
Publication Title
Germinal center B cell maintenance and differentiation are controlled by distinct NF-κB transcription factor subunits.
Sample Metadata Fields
No sample metadata fields
View Samples