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SRP152919
Mus musculus
3 Downloadable Samples
Illumina HiSeq 1500
Description
Memory CD4+ T helper (Th) cells are crucial for acquired immunity and protection from infectious microorganisms, and also drive pathogenesis of chronic inflammatory diseases, such as asthma. ST2hi memory-type Th2 cells have been identified as a pathogenic subpopulation capable of directly inducing eosinophilic airway inflammation. These ST2hi pathogenic Th2 cells produce large amounts of IL-5 upon stimulation via their TCR, but not in response to IL-33. In contrast, IL-33 alone induces cytokine production in ST2+ group 2 innate lymphoid cells (ILC2). We investigated the molecular mechanism that controls the innate function of IL-33-induced cytokine production, and identified a MAPK phosphatase Dusp10, as a key negative regulator of IL-33–induced cytokine production in Th2 cells. We found that Dusp10 is expressed by ST2hi pathogenic Th2 cells but not by ILC2, and Dusp10 expression inhibits IL-33-induced cytokine production by preventing GATA3 activity through inhibition of p38 MAPK phosphorylation. Strikingly, deletion of Dusp10 rendered ST2hi Th2 cells able to directly respond to IL-33 exposure and produce IL-5. Thus, DUSP10 constrains IL-33–induced cytokine production in ST2hi pathogenic Th2 cells by controlling p38-mediated GATA3 function. Overall design: Functions of Dusp10, a family of dual specificity protein phosphatase, are assessed by RNA-seq.
Publication Title
DUSP10 constrains innate IL-33-mediated cytokine production in ST2<sup>hi</sup> memory-type pathogenic Th2 cells.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Homo sapiens
- 6 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Activation of telomerase often endows cancer cells, but rarely normal somatic cells, with immortality. Especially, fetal lung fibroblasts are known to be hardly immortalized by TERT overexpression. We here established an immortal non-transformed lung fibroblast cell line only by TERT transfection, as well as an immortal transformed cell line by transfection of TERT and SV40 early antigens. Comparing the expression profiles of these cell lines with those of mortal cell strains with elongated lifespan after TERT transfection, 51 genes, including 19 upregulated and 32 downregulated, were explored to be the candidates responsible for regulation of cellular proliferation of lung fibroblasts. These included the genes previously reported to be involved in cellular proliferation, transformation, or self-renewal capacity, and those highly expressed in lung tissues obtained from patients with idiopathic pulmonary fibrosis or hypersensitivity pneumonitis. This set of lung fibrobrast cell lines/strains of identical genetic background with different proliferative capacity, mortal and immortal non-transformed fibroblasts may become useful model cells for research on lung fibroblast growth regulation and the candidate genes explored in this study may provide promising biomarkers or molecular targets of pulmonary fibrosis.
Publication Title
Exploration of the genes responsible for unlimited proliferation of immortalized lung fibroblasts.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 12 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Recent studies have shown that stem cell memory T (TSCM) cell-like properties are important for the successful adoptive immune therapy by the chimeric antigen receptor-engineered-T (CAR-T) cells. We previously reported that both human and murine activated T cells are converted into stem cell memory-like T (iTSCM) cells by co-culture with stromal OP9 cells expressing the NOTCH-ligand. However, the mechanism of NOTCH-mediated iTSCM reprogramming remains to be elucidated. Here, we report that the NOTCH/OP9 system efficiently converts conventional human CAR-T cells into TSCM-like CAR-T, “CAR-iTSCM” cells, and that the mitochondrial metabolic reprogramming plays a key role in this conversion. The NOTCH signals promote mitochondrial biogenesis and fatty acid synthesis during iTSCM formation, which are essential for the properties of iTSCM cells. We identified fork head box M1 (FOXM1) as a downstream target of NOTCH, which is responsible for these metabolic changes and the subsequent iTSCM differentiation. Like NOTCH-induced CAR-iTSCM cells, FOXM1-induced CAR-iTSCM cells possess superior antitumor potential compared to conventional CAR-T cells. We propose that the NOTCH- or FOXM1-driven CAR-iTSCM formation is an effective strategy for improving cancer immunotherapy.
Publication Title
The NOTCH-FOXM1 Axis Plays a Key Role in Mitochondrial Biogenesis in the Induction of Human Stem Cell Memory-like CAR-T Cells.
Sample Metadata Fields
Sex, Specimen part
View Samples- Homo sapiens
- 2 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
We investigated that gene expression profile of generated human iPS cells from cord blood cells using temperature sensitive sendai-virus vector.
Publication Title
Efficient generation of transgene-free human induced pluripotent stem cells (iPSCs) by temperature-sensitive Sendai virus vectors.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 8 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Screening for genes regulated by Etv2 within Flk-1+/PDGFRa+ ES derived mesoderm.Microarray analysis performed to screen for the candidate genes regulated by Etv2. TT2 ES cells differentiated on OP9 feeder cells were sorted using Flk-1 and PDGFRa antibodies.Gene expressions from these two populations were compared.
Publication Title
Etv2/ER71 induces vascular mesoderm from Flk1+PDGFRα+ primitive mesoderm.
Sample Metadata Fields
Cell line
View Samples- Mus musculus
- 4 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Screening for genes up in Etv2+ cells within Flk-1+ ES derived mesoderm
Publication Title
Etv2/ER71 induces vascular mesoderm from Flk1+PDGFRα+ primitive mesoderm.
Sample Metadata Fields
Cell line
View Samples- Mus musculus
- 18 Downloadable Samples
- Affymetrix Murine Genome U74A Version 2 Array (mgu74av2)
Description
Deregulated retinal angiogenesis directly cause vision loss in many ocular diseases, such as diabetic retinopathy and retinopathy of prematurity. To identify endothelial-specific genes expressed in angiogenic retinal vessels, we purified genetically labeled endothelial cells from Tie2-GFP transgenic mice and performed gene expression profiling using DNA microarray. To find out genes associated with angiogenesis, comparisons of microarray data were carried out between GFP-negative non-endothelial retinal cells and GFP-positive retinal endothelial cells in angiogenic P8 retina.
Publication Title
Sema3E-PlexinD1 signaling selectively suppresses disoriented angiogenesis in ischemic retinopathy in mice.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 4 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Four conditions of cultured CD8+ T cells were analyzed with Affymetrix HG-U133-Plus-2.0 microarrays.
Publication Title
Detection of self-reactive CD8⁺ T cells with an anergic phenotype in healthy individuals.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 12 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
In our experiments with a xenograft model, mouse-IFN (mIFN) treatment was suggested to exaggerate the antitumor effects of sorafenib on hepatocellular carcinoma in vivo.
Publication Title
The in vivo antitumor effects of type I-interferon against hepatocellular carcinoma: the suppression of tumor cell growth and angiogenesis.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 9 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
To develop more potent cell transplantation therapy for neurodegenerative disorder such as Parkinsons disease (PD), the condition of the host brain environment should be considered to improve the outcome of grafted neurons. However, we never know which condition of host brain environment is suitable and supportive for the donor cells. In addition, what endogenous factor(s) do contribute to improve the engraftment of donor cells in host brain? Therefore, the identification of such effective factor(s) strongly contribute to improve the overcome of cell transplantation therapy. Here, we constructed the experimental approach to identify the effective soluble factor(s) for cell-grafting by comparison between various parkinsonian mouse brain condition and transplantation outcome using induced pluripotent stem cell (iPSC)-derived dopaminergic (DA) neuron progenitors. According to our experimental approach, we have identified secreted peptide, neurexophilin 3 (NXPH3) that enhance the survival of grafted-iPSC-derived DA neurons. Grafted-iPSC-derived DA neurons were increased by local supplement of NXPH3 protein. In addition, the expression level of NXPH3 in putamen of PD patients was significantly decreased than that of normal controls by using postmortem samples. These findings would be expected to contribute the new experimental strategy to indentify the endogenous effective factors for cell-grafting as in vivo application of stem cell technology.
Publication Title
Identification of Neurexophilin 3 as a Novel Supportive Factor for Survival of Induced Pluripotent Stem Cell-Derived Dopaminergic Progenitors.
Sample Metadata Fields
Specimen part
View Samples