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GSE15955
Mus musculus
4 Downloadable Samples
Description
STAT3 is a pleiotropic transcription factor with important functions in cytokine signalling in a variety of tissues. However, the role of STAT3 in the intestinal epithelium is not well understood. Here we demonstrate that development of colonic inflammation is associated with the induction of STAT3 activity in intestinal epithelial cells (IEC). Studies in genetically engineered mice showed that epithelial STAT3 activation in DSS colitis is dependent on IL-22 rather than IL-6. IL-22 was secreted by colonic CD11c+ cells in response to Toll-like receptor stimulation. Conditional knockout mice with an IEC specific deletion of STAT3 activity were highly susceptible to experimental colitis, indicating that epithelial STAT3 regulates gut homeostasis. STAT3IEC-KO mice, upon induction of colitis, showed a striking defect of epithelial restitution. Gene chip analysis indicated that STAT3 regulates the cellular stress response, apoptosis and pathways associated with wound healing in IEC. Consistently, both IL-22 and epithelial STAT3 were found to be important in wound-healing experiments in vivo. In summary, our data suggest that intestinal epithelial STAT3 activation regulates immune homeostasis in the gut by promoting IL-22-dependent mucosal wound healing.
Publication Title
STAT3 links IL-22 signaling in intestinal epithelial cells to mucosal wound healing.
Sample Metadata Fields
Specimen part
View Samples- Gallus gallus, Mus musculus
- 4 Downloadable Samples
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
The transcription factor prospero homeobox protein 1 is a direct target of SoxC proteins during developmental vertebrate neurogenesis.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 4 Downloadable Samples
Description
The HMG-domain containing SoxC transcription factors Sox4 and Sox11 are expressed in the vertebrate central nervous system in neuronal precursors and neuroblasts. They are required during early stages of neurogenesis.
Publication Title
The transcription factor prospero homeobox protein 1 is a direct target of SoxC proteins during developmental vertebrate neurogenesis.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 4 Downloadable Samples
Description
Plasmacytoid dendritic cells (pDC) efficiently produce large amounts of type I interferon in response to TLR7 and TLR9 ligands, whereas conventional DCs (cDC) predominantly secrete high levels of the cytokines IL-10 and IL-12. The molecular basis underlying this distinct phenotype is not well understood. Here, we identified the MAPK phosphatase Dusp9/MKP-4 by transcriptome analysis as selectively expressed in pDC, but not cDC. We confirmed the constitutive expression of Dusp9 at the protein level in pDC generated in vitro by culture with Flt3L and ex vivo in sorted splenic pDC. Dusp9 expression was low in B220- bone marrow precursors and was up-regulated during pDC differentiation, concomitant with established pDC markers. Higher expression of Dusp9 in pDC correlated with impaired phosphorylation of the MAPK ERK1/2 upon TLR9 stimulation. Notably, Dusp9 was not expressed at detectable levels in human pDC, although these displayed similarly impaired activation of ERK1/2 MAPK compared to cDC. Enforced retroviral expression of Dusp9 in mouse GM-CSF-induced cDC increased the expression of TLR7/9-induced IL-12p40 and IFNwhereas IL-10 levels were diminished. Taken together, our results suggest that the species-specific, selective expression of Dusp9 in murine pDC contributes to the differential cytokine/interferon output of pDC and cDC.
Publication Title
Selective Expression of the MAPK Phosphatase Dusp9/MKP-4 in Mouse Plasmacytoid Dendritic Cells and Regulation of IFN-β Production.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 31 Downloadable Samples
Description
Loss and heterozygosity for NDR1 predisposes mice to T-cell lymphoma development. To analyze mechanisms of tumor development in these mice chemically (ENU)-induced tumors were collected and RNA was extracted.
Publication Title
Ablation of the kinase NDR1 predisposes mice to the development of T cell lymphoma.
Sample Metadata Fields
Sex, Specimen part, Disease, Treatment
View Samples- Mus musculus
- 5 Downloadable Samples
Description
We have analyzed the transcript expression levels in Dicer knock-out embryonic stem (ES) cells 24 hours after transfection with either control siRNA agains Renilla luciferase or miRNA Mimics (Dharmacon) of mmu-miR-290 cluster members in order to identify primary targets of miR-290 cluster miRNAs.
Publication Title
MicroRNAs control de novo DNA methylation through regulation of transcriptional repressors in mouse embryonic stem cells.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 13 Downloadable Samples
Description
OBF1, also known as Bob.1 or OCA-B, is a B lymphocyte-specific transcription factor which coactivates Oct1 and Oct2 on B cell specific promoters. So far, the function of OBF1 has been mainly identified in late stage B cell populations. The central defect of OBF1 deficient mice is a severely reduced immune response to T cell-dependent antigens and a lack of germinal center formation in the spleen. Relatively little is known about a potential function of OBF1 in developing B cells. Here we have generated transgenic mice overexpressing OBF1 in B cells under the control of the immunoglobulin heavy chain promoter and enhancer. Surprisingly, these mice have greatly reduced numbers of follicular B cells in the periphery and have a compromised immune response. Furthermore, B cell differentiation is impaired at an early stage in the bone marrow. A first block is observed during B cell commitment and a second differentiation block is seen at the large preB2 cell stage. The cells that succeed to escape the block and to differentiate into mature B cells have post-translationally downregulated the expression of transgene, indicating that expression of OBF1 beyond the normal level early in B cell development is deleterious. Indeed ID3, which is a negative regulator of B cell differentiation, is upregulated in the EPLM and preB cells of the transgenic mice. Furthermore ID3 promoter contains an octamer site suggesting that it is a potential OBF-1 direct target gene. These results provide evidence that OBF1 expression has to be tightly regulated in early B cells to allow efficient B lymphocyte differentiation.
Publication Title
No associated publication
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 54 Downloadable Samples
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Exploiting microRNA and mRNA profiles generated in vitro from carcinogen-exposed primary mouse hepatocytes for predicting in vivo genotoxicity and carcinogenicity.
Sample Metadata Fields
Specimen part, Compound
View Samples- Mus musculus, Homo sapiens
- 94 Downloadable Samples
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Integrating factor analysis and a transgenic mouse model to reveal a peripheral blood predictor of breast tumors.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus, Homo sapiens
- 231 Downloadable Samples
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Experimentally derived metastasis gene expression profile predicts recurrence and death in patients with colon cancer.
Sample Metadata Fields
Sex, Age, Disease stage, Race
View Samples