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GSE62079
Homo sapiens
2 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Background: Identification and purification of cancer stem cells (CSCs) lead to new therapeutic targets; however, there has been no study to identify and isolated pancreatic neuroendocrine tumor (pNET) CSC. Therefore the clinical significance and its target remain unknown. This study aimed to identify pNET CSCs and characterize therapeutic candidate for pNET CSCs. Methods: We isolated CSCs sorting by ALDH activity in pNET surgical section and cell lines. We verified whether these cells have the property of stemness in vivo and in vitro. Additionally in order to acquire CSC gene profile, genome-wide gene expression profiles were investigated using a microarray technique. Results: ALDHhigh cells, but not control bulk cells, formed spheres, proliferated in hypoxia as well as normoxia and promoted cell motility, which are features of CSCs. Injection of as few as 10 ALDHhigh cells led to subcutaneous tumor formation, and 105 ALDHhigh cells established metastases but not control bulk cells in mice. Comprehensive gene expression analysis revealed that genes associated with mesenchymal stem cell, including CD73, and epithelial-mesenchymal transition (EMT) were overexpressed in ALDHhigh cells. APCP, which is CD73 inhibitor, inhibited sphere formation and cell motility in ALDHhigh cells in vitro, and tumor growth inhibition were observed in ALDHhigh cells in vivo. Conclusions: We identified ALDHhigh cells of pNET and elucidated that they have stemness property. Furthermore we identified CD73 as a target of ALDHhigh cells. CD73 is a promising novel target of pNET CSCs.
Publication Title
CD73 as a therapeutic target for pancreatic neuroendocrine tumor stem cells.
Sample Metadata Fields
Cell line
View Samples- Mus musculus
- 4 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
We report that Tripartite motif-containing 33 (Trim33), a protein that was previously associated with TGF-beta signaling, determines the pathogenic function of Th17 cells. Trim33 deficiency in T cells resulted in resistance to an autoimmune disease model. Lack of Trim33 did not impact TGF-beta signaling in mediating Foxp3 gene expression but greatly reduced TGF-beta induction of IL-17 production during Th17 cell differentiation. Importantly, we found TGF-beta not only increased IL-17 but also suppressed IL-10 expression; absence of Trim33 or Smad2 but not Smad4 in T cells enhanced IL-10 expression. In a Smad2-dependent manner, Trim33 was recruited to Il17 and Il10 gene loci and was crucial in appropriate histone modification accompanying Th17 differentiation.
Publication Title
Trim33 mediates the proinflammatory function of Th17 cells.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 4 Downloadable Samples
Illumina HiSeq 2000
Description
Substantial evidence supports the hypothesis that enhancers are critical regulators of cell type determination, orchestrating both positive and negative transcriptional programs; however, the basic mechanisms by which enhancers orchestrate interactions with cognate promoters during activation and repression events remain incompletely understood. Here we report the required actions of the LIM domain binding protein, LDB1/CLIM2/NLI, interacting with the enhancer binding protein, ASCL1, to mediate looping to target gene promoters and target gene regulation in corticotrope cells. LDB1-mediated enhancer:promoter looping appears to be required for both activation and repression of these target target gene promoter genes. While LDB1-dependend activated genes are regulated at the level of transcriptional initiation, the LDB1-dependent repressed transcription units appear to be regulated primarily at the level of promoter pausing, with LDB1 regulating recruitment of MTA2, a component of the NuRD complex, on these negative enhancers, required for the repressive enhancer function. These results indicate that LDB1-dependent looping events can deliver repressive cargo to cognate promoters to mediate promoter pausing events in a pituitary cell type. Overall design: Global Run On (GRO) assay followed by high throughput sequencing (GRO-seq)
Publication Title
Enhancer-bound LDB1 regulates a corticotrope promoter-pausing repression program.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 49 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Background & Aims: The recurrence determines the postoperative prognosis of patients with hepatocellular carcinoma (HCC). It is unknown whether de novo HCCs derive from the liver with disability of an organic anion transport. This study was designed to elucidate the link between such transporters and the multicentric occurrence (MO) after radical hepatectomy.
Publication Title
Mitochondrial metabolism in the noncancerous liver determine the occurrence of hepatocellular carcinoma: a prospective study.
Sample Metadata Fields
Specimen part, Disease, Disease stage, Subject
View Samples- Mus musculus
- 20 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Expression profiles in mouse liver exposed to long-term gamma-irradiation were examined to assess in vivo effects of low dose-rate radiation. Three groups of male C57BL/6J mice were exposed to whole body irradiation at dose-rates of 17-20 mGy/day, 0.86-1.0 mGy/day or 0.042-0.050 mGy/day for 401-485 days (cumulative doses were approximately 8 Gy, 0.4 Gy or 0.02 Gy, respectively).
Publication Title
Gene expression profiles in mouse liver after long-term low-dose-rate irradiation with gamma rays.
Sample Metadata Fields
Sex, Specimen part
View Samples- Mus musculus
- 8 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
For the clinical treatment of chronic obstructive pulmonary disease (COPD), it is important not only to improve the airflow limitation by bronchodilation but also to suppress emphysema by controlling inflammation. In this study, we have screened for compounds that prevent elastase-induced airspace enlargement in mice from medicines already used clinically. Mepenzolate bromide, a muscarinic antagonist used to treat gastrointestinal disorders was selected. Intratracheal administration or inhalation of mepenzolate bromide decreased the severity of elastase-induced airspace enlargement, alteration of lung mechanics and respiratory dysfunction. While mepenzolate bromide showed bronchodilatory activity, most of other muscarinic antagonists tested did not improve the elastase-induced pulmonary disorders. Mepenzolate bromide suppressed elastase-induced pulmonary inflammatory responses and production of superoxide anions, and reduced the level of cigarette smoke-induced airspace enlargement and alteration of lung mechanics. Based on these results, we propose that this drug is therapeutically effective for COPD as a consequence of both its anti-inflammatory and bronchodilatory activities.
Publication Title
Mepenzolate bromide displays beneficial effects in a mouse model of chronic obstructive pulmonary disease.
Sample Metadata Fields
Treatment, Time
View Samples- Homo sapiens
- 4 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Purpose: Pancreatic neuroendocrine tumors (PanNETs) have considerable malignant potential. Frequent somatic mutations and loss of DAXX protein expression have been frequently found in PanNETs. DAXX is known as a transcriptional repressor, however, molecular functions underlying loss of DAXX remain unclear in PanNETs.
Publication Title
Tumor suppressor functions of DAXX through histone H3.3/H3K9me3 pathway in pancreatic NETs.
Sample Metadata Fields
Treatment
View Samples- Homo sapiens
- 9 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Fibroadenomas are the most common benign breast tumors in women under 30. Unlike their malignant counterparts, relatively molecular profiling has been done on fibroadenomas. Here we performed gene expression profiling on ten fibroadenomas in order to better characterize these tumors. Through targeted amplicon sequencing, we have found that six of these tumors have MED12 mutations. We show that the MED12 mutations, among others, are associated with activated estrogen signaling, as well as increased invasiveness through upregulation of ECM remodelling genes.
Publication Title
Exome sequencing identifies highly recurrent MED12 somatic mutations in breast fibroadenoma.
Sample Metadata Fields
Age
View Samples- Homo sapiens
- 4 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Anti-angiogenic therapy is initially effective for several solid tumors including hepatocellular carcinoma (HCC); however, they finally relapse and progress, resulting in poor prognosis. We here established in vivo drug-tolerant subclones of human HCC cells by long-term treatment with vascular endothelial growth factor receptor (VEGFR) inhibitor and serial transplantation in immunocompromised mice (total 12 months), and then compared them with the parental cells in molecular and biological features. Gene expression profiles elucidated a G-actin monomer binding protein thymosin 4 (T4) as one of the genes enriched in the resistant cancer cells relative to the initially sensitive ones. Highlighting epigenetic alterations involved in drug resistance, we revealed that T4 could be aberrantly expressed following demethylation of DNA and active modification of histone H3 at the promoter region. Ectopic overexpression of T4 in HCC cells could significantly enhance sphere-forming capacities and infiltrating phenotypes in vitro, and promote growth of tumors refractory to the VEGFR mutltikinase inhibitor sorafenib in vivo. Clinically, sorafenib failed to improve the progression-free survival in patients with T4-high HCC, indicating that T4 expression could be available as a surrogate marker of susceptibility to this drug. This study suggests that T4 expression triggered by epigenetic alterations could contribute to the development of resistance to anti-angiogenic therapy by the acquisition of stemness, and that epigenetic control might be one of the key targets to regulate the resistance in HCC.
Publication Title
Acquired Resistance with Epigenetic Alterations Under Long-Term Antiangiogenic Therapy for Hepatocellular Carcinoma.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Homo sapiens
- 3 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
Human pluripotent stem cells (hPSC) generate hematopoietic progenitor cells (HPC), but fail to engraft xenograft models, which is a hallmark feature of adult/somatic hematopoietic stem cells (HSC) from human donors. Progress to derive hPSC-derived HSCs has relied on cell autonomous approaches that force expression of transcription factors (TF), however the role of bone marrow (BM) niche remains poorly understood. Here, we quantified a failure of hPSC-HPCs to survive even in the first 24 h upon transplantation into the BM. Across several hPSC-HPC differentiation methodologies, we identified the lack of CXCR4 expression and network function. Ectopic CXCR4 conferred CXCL12-dependent signaling of hPSC-HPCs in biochemical assays and increased migration/chemotaxis and progenitor capacity, as well as survival and proliferation following transplantation in vivo. In addition, hPSC-HPCs forced to express CXCR4 demonstrated a transcriptional shift toward somatic HPCs, but this approach failed to produce long-term HSC engraftment. Our results reveal that independent of differentiation methods, networks involving CXCR4 should be targeted to generate HSCs with in vivo function from hPSCs.
Publication Title
CXCL12/CXCR4 Signaling Enhances Human PSC-Derived Hematopoietic Progenitor Function and Overcomes Early In Vivo Transplantation Failure.
Sample Metadata Fields
Specimen part
View Samples