Bone morphogenic proteins (BMPs) function in virtually all tissues with cell-type specific outcomes. Since there are a relatively small number of BMP receptors this exquisite signaling specificity requires additional molecules to regulate the output of this pathway. We demonstrated that the receptor tyrosine kinase MuSK that is selectively expressed in muscle and plays a critical role in synapse formation and maintenance binds to BMP4 and related BMPs. Since BMPs regulate the transcription of a set of genes, we performed microarrays for wild-type and MuSK null muscle cells to test if MuSK regulates BMP responses in muscle cells.
MuSK is a BMP co-receptor that shapes BMP responses and calcium signaling in muscle cells.
No sample metadata fields
View SamplesThe dual bromodomain protein Brd2 is closely related to the basal transcription factor TAFII250, which is essential for cyclin A transactivation and mammalian cell cycle progression. In transgenic mice, constitutive lymphoid expression of Brd2 causes a malignancy most similar to human diffuse large B cell lymphoma. We compare the genome-wide transcriptional expression profiles of these lymphomas with those of proliferating and resting normal B cells. Transgenic tumors reproducibly show differential expression of a large number of genes important for cell cycle control and lymphocyte biology; expression patterns are either tumor-specific or proliferation-specific. Several of their human orthologs have been implicated in human lymphomagenesis. Others correlate with human disease survival time. BRD2 is underexpressed in some subtypes of human lymphoma and these subtypes display a number of similarities to the BRD2-mediated murine tumors. We illustrate with a high degree of detail that cancer is more than rampant cellular proliferation, but involves the additional transcriptional mobilization of many genes, some of them poorly characterized, which show a tumor-specific pattern of gene expression.
Tumor-specific and proliferation-specific gene expression typifies murine transgenic B cell lymphomagenesis.
Specimen part
View SamplesPyrazinamide (PZA) is one of the first line antibiotics used for the treatment of tuberculosis (TB). we have used human monocyte and a mouse model of pulmonary TB to investigate whether treatment with PZA, in addition to its known anti-mycobacterial properties, modulate the host immune response during Mycobacterium tuberculosis (Mtb) infection.
Host targeted activity of pyrazinamide in Mycobacterium tuberculosis infection.
Specimen part, Treatment, Time
View SamplesPathogen-associated molecular patterns decisively influence antiviral immune responses, whereas the contribution of endogenous signals of tissue damage, also known as damage-associated molecular patterns or alarmins, remains ill-defined. We show that interleukin-33 (IL-33), an alarmin released from necrotic cells, is necessary for potent CD8+ T cell (CTL) responses to replicating, prototypic RNA and DNA viruses in mice. IL-33 signaled through its receptor on activated CTLs, enhanced clonal expansion in a MyD88-dependent, CTL-intrinsic fashion, determined polyfunctional effector cell differentiation and was necessary for virus control. Moreover, recombinant IL-33 augmented vaccine-induced CTL responses. Radio-resistant cells of the splenic T cell zone produced IL-33, and efficient CTL responses required IL-33 from radio-resistant cells but not from hematopoietic cells. Thus, alarmin release by radio-resistant cells orchestrates protective antiviral CTL responses.
The alarmin interleukin-33 drives protective antiviral CD8⁺ T cell responses.
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
The alarmin IL-33 promotes regulatory T-cell function in the intestine.
Specimen part
View SamplesIL-23 negatively regulates St2 and Gata3 expression in intestinal CD4+ T cells
The alarmin IL-33 promotes regulatory T-cell function in the intestine.
Specimen part
View SamplesGenomic and expression profiling using 38K BAC array-CGH and Illumina HT-12 beadchips were performed on 97 diploid invasive breast tumors to assess the impact of gene dosage on gene expression patterns and the effect of other mechanisms on transcriptional levels. Patient stratification was performed according to axillary lymph node status (node-negative, pN0; node-positive, pN1) and overall survival (>8-year survivors; breast cancer-specific mortality within 8 years of diagnosis). Array-CGH results was validated by FISH using tumors showing HER2/neu gene amplification and expression profiling was confirmed using qPCR for 16 transcripts.
Clinical implications of gene dosage and gene expression patterns in diploid breast carcinoma.
Disease, Disease stage
View SamplesGenomic and expression profiling using 38K BAC array-CGH and Illumina HT-12 beadchips were performed on 97 diploid invasive breast tumors to assess the impact of gene dosage on gene expression patterns and the effect of other mechanisms on transcriptional levels. Patient stratification was performed according to axillary lymph node status (node-negative, pN0; node-positive, pN1) and overall survival (>8-year survivors; breast cancer-specific mortality within 8 years of diagnosis). Array-CGH results was validated by FISH using tumors showing HER2/neu gene amplification and expression profiling was confirmed using qPCR for 16 transcripts.
Clinical implications of gene dosage and gene expression patterns in diploid breast carcinoma.
Disease, Disease stage
View SamplesTranscriptomic profiling of human breast tumors.
Clinical implications of gene dosage and gene expression patterns in diploid breast carcinoma.
Age, Specimen part
View SamplesIL-4/GFP- enhanced transcript (4Get) reporter mice were infected with 200 PFU of Influenza A virus PR8 strain. At day 3 of infection, mediastinal lymph nodes were harvested and GFP+ cells sorted and separated by their ability to bind a CD1d-tetramer (Tet+ n=133 , Tet- n=109 ). Single-cell RNA-Seq was used to identify subpopulations of IL-4 producing cells. Single-cell transcriptomes were clustered using Seurat and differentially expressed genes within each cluster were used to resolve IL-4+ subpopulations and aid in defining their role in initiating B cell immunity during influenza infection. Overall design: Examine cells involved in accute viral response in the lymph node after influenza infection
Initiation of Antiviral B Cell Immunity Relies on Innate Signals from Spatially Positioned NKT Cells.
Specimen part, Subject
View Samples