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GSE18198
Homo sapiens
6 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
NOTCH proteins regulate signaling pathways involved in cellular differentiation, proliferation and death. Overactive Notch signaling as been observed in numerous cancers and has been extensively studied in the context of T-cell acute lymphoblastic leukemia (T-ALL) where more than 50% of pateints harbour mutant NOTCH1. Small molecule modulators of these proteins would be important for understanding the role of NOTCH proteins in malignant and normal biological processes.
Publication Title
Direct inhibition of the NOTCH transcription factor complex.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Homo sapiens
- 250 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
The purpose of this study was to characterize the transcriptional effects induced by subcutaneous IFN-beta-1b treatment (Betaferon, 250 g every other day) in patients with relapsing-remitting form of multiple sclerosis (MS).
Publication Title
Long-term genome-wide blood RNA expression profiles yield novel molecular response candidates for IFN-beta-1b treatment in relapsing remitting MS.
Sample Metadata Fields
Sex
View Samples- Rattus norvegicus
- 24 Downloadable Samples
- Affymetrix Rat Gene 1.0 ST Array (ragene10st)
Description
In addition to gaining knowledge on in vivo miRNA responses to formaldehyde, we set out to relate these miRNA responses to transcriptional profiles modified by formaldehyde. Rats were exposed by inhalation to either 0 or 2 ppm formaldehyde (6 hours/day) for 28 days. Genome-wide transcriptional profiles and associated signaling pathways were assessed within the nasal respiratory mucosa and circulating mononuclear white blood cells (WBC).
Publication Title
Formaldehyde-associated changes in microRNAs: tissue and temporal specificity in the rat nose, white blood cells, and bone marrow.
Sample Metadata Fields
Sex, Specimen part, Treatment, Time
View Samples- Mus musculus
- 6 Downloadable Samples
Illumina HiSeq 2000
Description
High grade serous carcinoma (HGSC) arising from either the fallopian tube or ovary has a poor prognosis primarily due to its early dissemination throughout the abdominal cavity. Genomic and proteomic approaches have provided snapshots of the proteogenomics of ovarian cancer (OvCa)1,2, but a systematic examination of both the tumor and stromal compartments is critical to understanding OvCa metastasis. We developed a label-free proteomic workflow to analyze as few as 5,000 formalin-fixed, paraffin embedded cells microdissected from each compartment. The tumor proteome was comparatively stable during progression from in situ lesions to metastatic disease; however, the metastasis-associated stroma was characterized by a highly conserved proteomic signature, prominently including the methyltransferase nicotinamide N-methyltransferase (NNMT) and the proteins it regulates. Stromal NNMT expression was necessary and sufficient for several functional aspects of the cancer associated fibroblast (CAF) phenotype, including the expression of CAF markers and the secretion of cytokines and oncogenic extracellular matrix. Stromal NNMT supported OvCa migration, proliferation, and in vivo growth and metastasis. Expression of NNMT in CAFs led to a depletion of S-adenosyl methionine (SAM) and a reduction in histone methylation associated with extensive gene expression changes in the tumor stroma. This work supports the use of ultra-low input proteomics to identify candidate drivers of disease phenotypes and reveals that NNMT is a central, metabolic regulator of CAF differentiation and cancer progression in the stroma and a novel treatment target. Overall design: Three biological replicates of normal murine 3T3 fibroblasts expressing either control or NNMT overexpression construct were grown for 48 hours in physiological levels of methionine before RNA was collected and sequenced to identify genes differentially regulated in response to NNMT.
Publication Title
Proteomics reveals NNMT as a master metabolic regulator of cancer-associated fibroblasts.
Sample Metadata Fields
Cell line, Subject
View Samples- Mus musculus
- 15 Downloadable Samples
- Illumina HiSeq 2500
Description
RNA sequencing of ILC2s sorted from ß2 adrenergic receptor agonist-treated and non-treated mice Overall design: RNAs of ILC2s sorted as KLRG1+CD127+CD90+Lin-CD45+ from ß2 adrenergic receptor agonist-treated and non-treated mice mLNs 4 days post N. brasiliensis infection were analyzed
Publication Title
β<sub>2</sub>-adrenergic receptor-mediated negative regulation of group 2 innate lymphoid cell responses.
Sample Metadata Fields
Specimen part, Cell line, Treatment, Subject
View Samples- Homo sapiens
- 95 Downloadable Samples
- Illumina HiSeq 2500
Description
We provide a map of human ILC heterogeneity across multiple anatomical sites. Tissue-specific distinctions are particularly apparent for ILC1 populations, whose distribution was markedly altered in obesity or aging. Furthermore, the degree of ILC1 population hetero- geneity differed substantially in lymphoid versus mucosal sites. Together, these analyses comprise a comprehensive characterization of the spatial and temporal dynamics regulating the anatomical distri- bution, subset heterogeneity, and functional poten- tial of ILCs in non-diseased human tissues. Overall design: We present a quantitative analysis of ILC distribution and heterogeneity in lymphoid, mucosal, and metabolic tissues obtained from a diverse cohort of 44 previously non-diseased organ donors over a wide range of ages and body mass indexes (BMIs).
Publication Title
Spatial and Temporal Mapping of Human Innate Lymphoid Cells Reveals Elements of Tissue Specificity.
Sample Metadata Fields
Specimen part, Subject
View Samples- Mus musculus
- 28 Downloadable Samples
- Illumina HiSeq 2500
Description
The type 2 cytokines interleukin (IL)-4, IL-5, IL-9 and IL-13 play critical roles in stimulating innate and adaptive immune responses required for resistance to helminth infection and promotion of allergic inflammation, metabolic homeostasis and tissue repair. Group 2 innate lymphoid cells (ILC2s) are a potent source of type 2 cytokines and while significant advances have been made in understanding the cytokine milieu that promotes ILC2 responses, there are fundamental gaps in knowledge regarding how ILC2 responses are regulated by other stimuli. In this report, we demonstrate that ILC2s in the gastrointestinal tract co-localize with cholinergic neurons that express the neuropeptide neuromedin U (NMU). In contrast to other hematopoietic cells, ILC2s selectively express the NMU receptor 1 (NMUR1). In vitro stimulation of ILC2s with NMU induced rapid cell activation, proliferation and secretion of type 2 cytokines IL-5, IL-9 and IL-13 that was dependent on cell-intrinsic expression of NMUR1 and Gaq protein. In vivo administration of NMU triggered potent type 2 cytokine responses characterized by ILC2 activation, proliferation and eosinophil recruitment that was associated with accelerated expulsion of the gastrointestinal nematode Nippostrongylus brasiliensis or induction of lung inflammation. Conversely, worm burden was higher in Nmur1-/- mice compared to control mice. Further, use of gene-deficient mice and adoptive cell transfer experiments revealed that ILC2s were necessary and sufficient to mount NMU-elicited type 2 cytokine responses. Together, these data indicate that the NMU-NMUR1 neuronal signaling circuit provides a selective and previously unrecognized mechanism through which the enteric nervous system and innate immune system integrate to promote rapid type 2 cytokine responses that can induce anti-microbial, inflammatory and tissue-protective type 2 responses at mucosal sites. Overall design: To assess changes in gene expression in ILC2s due to NMU treatment, RNAseq was performed on 3 samples from NMU-treated mice and 4 samples from PBS-treated mice.
Publication Title
The neuropeptide neuromedin U stimulates innate lymphoid cells and type 2 inflammation.
Sample Metadata Fields
Specimen part, Cell line, Treatment, Subject
View Samples- Mus musculus
- 18 Downloadable Samples
- Illumina HiSeq 2500
Description
The type 2 cytokines interleukin (IL)-4, IL-5, IL-9 and IL-13 play critical roles in stimulating innate and adaptive immune responses required for resistance to helminth infection and promotion of allergic inflammation, metabolic homeostasis and tissue repair. Group 2 innate lymphoid cells (ILC2s) are a potent source of type 2 cytokines and while significant advances have been made in understanding the cytokine milieu that promotes ILC2 responses, there are fundamental gaps in knowledge regarding how ILC2 responses are regulated by other stimuli. In this report, we demonstrate that ILC2s in the gastrointestinal tract co-localize with cholinergic neurons that express the neuropeptide neuromedin U (NMU). In contrast to other hematopoietic cells, ILC2s selectively express the NMU receptor 1 (NMUR1). In vitro stimulation of ILC2s with NMU induced rapid cell activation, proliferation and secretion of type 2 cytokines IL-5, IL-9 and IL-13 that was dependent on cell-intrinsic expression of NMUR1 and Gaq protein. In vivo administration of NMU triggered potent type 2 cytokine responses characterized by ILC2 activation, proliferation and eosinophil recruitment that was associated with accelerated expulsion of the gastrointestinal nematode Nippostrongylus brasiliensis or induction of lung inflammation. Conversely, worm burden was higher in Nmur1-/- mice compared to control mice. Further, use of gene-deficient mice and adoptive cell transfer experiments revealed that ILC2s were necessary and sufficient to mount NMU-elicited type 2 cytokine responses. Together, these data indicate that the NMU-NMUR1 neuronal signaling circuit provides a selective and previously unrecognized mechanism through which the enteric nervous system and innate immune system integrate to promote rapid type 2 cytokine responses that can induce anti-microbial, inflammatory and tissue-protective type 2 responses at mucosal sites. Overall design: Transcriptional differences between ILC2s and ILC3s were determined by RNAseq using 3 ILC2 samples and 3 ILC3 samples.
Publication Title
The neuropeptide neuromedin U stimulates innate lymphoid cells and type 2 inflammation.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Mus musculus
- 8 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Parietal epithelial cells (PECs) are crucially involved in the pathogenesis of rapidly progressive glomerulonephritis (RPGN) as well as in focal and segmental glomerulosclerosis (FSGS). In this study, transgenic mouse lines were used to isolate pure, genetically tagged primary cultures of PECs or podocytes using FACsorting. By this approach, the morphology of primary glomerular epithelial cells in culture could be resolved: Primary podocytes formed either large cells with intracytoplasmatic extensions or smaller spindle shaped cells, depending on specific culture conditions. Primary PECs were small and exhibited a spindle-shaped or polygonal morphology. In the very early phases of primary culture, rapid changes in gene expression (e.g. of WT-1 and Pax-2) were observed. However, after prolonged culture primary PECs and podocytes still segregated clearly in a transcriptome analysis - demonstrating that the origin of primary cell cultures is important. Of the classical markers, synaptopodin and podoplanin expression were differentially regulated the most in primary PEC and podocyte cultures. However, no expression of any endogenous gene allowed to differentiate between the two cell types in culture. Finally, we show that the transcription factor WT1 is also expressed by PECs. In summary, genetic tagging of PECs and podocytes is a novel and necessary tool to derive pure primary cultures with proven origin. These cultures will be a powerful tool for the emerging field of parietal epithelial cell biology.
Publication Title
Primary cultures of glomerular parietal epithelial cells or podocytes with proven origin.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 3 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Transcriptomes of differentiated cells of the conditionally immortalized mouse podocyte cell line SVI (Schiwek et al., Kidney Int. 66: 91-101, 2004) were determined as described in Kabgani et al. (PLoS One 7:e34907, 2012).
Publication Title
Primary cultures of glomerular parietal epithelial cells or podocytes with proven origin.
Sample Metadata Fields
Specimen part, Cell line
View Samples