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GSE57625
Homo sapiens
7 Downloadable Samples
Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Mammalian mRNAs are generated by complex and coordinated biogenesis pathways and acquire 5'-end m7G caps that play fundamental roles in processing and translation. Here we show that several selenoprotein mRNAs are not recognized efficiently by translation initiation factor eIF4E because they bear a hypermethylated cap. This cap modification is acquired via a 5end maturation pathway similar to that of the small nucle(ol)ar RNAs (sn- and snoRNAs). Our findings also establish that the trimethylguanosine synthase 1 (Tgs1) interacts with selenoprotein mRNAs for cap hypermethylation and that assembly chaperones and core proteins devoted to sn- and snoRNP maturation contribute to recruiting Tgs1 to selenoprotein mRNPs. We further demonstrate that the hypermethylated-capped selenoprotein mRNAs localize to the cytoplasm, are associated with polysomes and thus translated. Moreover, we found that the activity of Tgs1, but not of eIF4E, is required for the synthesis of the GPx1 selenoprotein in vivo.
Publication Title
Hypermethylated-capped selenoprotein mRNAs in mammals.
Sample Metadata Fields
Cell line
View Samples- Homo sapiens
- 66 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
To examine the impact of tumors on the immune system, we compared global gene expression profiles of peripheral blood T cells from previously untreated patients with B cell chronic lymphocytic leukemia (CLL) with those from age-matched healthy donors. Although the cells analyzed were not part of the malignant clone, analysis revealed differentially expressed genes, mainly involved in cell differentiation in CD4 cells and defects in cytoskeleton formation, vesicle trafficking, and cytotoxicity in CD8 cells of the CLL patients. In coculture experiments using CLL cells and T cells from healthy allogeneic donors, similar defects developed in both CD4 and CD8 cells. These changes were induced only with direct contact and were not cytokine mediated. Identification of the specific pathways perturbed in the T cells of cancer-bearing patients will allow us to assess steps to repair these defects, which will likely be required to enhance antitumor immunity.
Publication Title
Chronic lymphocytic leukemia cells induce changes in gene expression of CD4 and CD8 T cells.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 12 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Previous studies in our laboratory demonstrated that the azurophil granule protease neutrophil elastase (NE) cleaves PML-RARA (PR), the fusion protein that initiates acute promyelocytic leukemia (APL). Further, NE deficiency reduces the penetrance of APL in a murine model of this disease. We therefore predicted that NE-mediated PR cleavage might be important for its ability to initiate APL. To test this hypothesis, we generated a mouse expressing NE-resistant PR. These mice developed APL indistinguishable from wild type PR, but with significantly reduced latency (median leukemia-free survival of 274 days versus 473 days for wild type PR, p<0.001). Resistance to proteolysis may increase the abundance of full length PR protein in early myeloid cells, and our previous data suggested that non-cleaved PR may be less toxic to early myeloid cells. Together, these effects appear to increase the leukemogenicity of NE-resistant PR, contrary to our previous prediction. We conclude that NE deficiency may reduce APL penetrance via indirect mechanisms that are still NE dependent.
Publication Title
A protease-resistant PML-RAR{alpha} has increased leukemogenic potential in a murine model of acute promyelocytic leukemia.
Sample Metadata Fields
Cell line
View Samples- Mus musculus
- 20 Downloadable Samples
- Affymetrix Mouse Expression 430A Array (moe430a)
Description
Murine pancreatic beta cell line MIN6 was growth at two different concentrations of glucose (22,2 and 5,5 mM of glucose), 37C, 5% CO2 and was treated at four different concentrations of human amylin (0, 1, 10 and 20 uM) during three different times (2, 12 and 24 hours)
Publication Title
Impairment of the ubiquitin-proteasome pathway is a downstream endoplasmic reticulum stress response induced by extracellular human islet amyloid polypeptide and contributes to pancreatic beta-cell apoptosis.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 8 Downloadable Samples
NextSeq 500
Description
This analysis represents the first comprehensive sampling of germ cells in the developing testis over time, at high-resolution, single-cell depth. From these analyses, we have not only revealed novel genetic regulatory signatures of murine germ cells over time, but have also demonstrated that cell types positive for a single marker gene have the capacity to change dramatically during testis maturation, and therefore cells of a particular “identity” may differ significantly from postnatal to adult life. Overall design: Single-cell suspensions of mammalian testes ranging from PND6 to adult were processed for single-cell RNAseq (10x Genomics Chromium) and libraries were sequenced on a NextSeq500 (Illumina).
Publication Title
Dynamic transcriptome profiles within spermatogonial and spermatocyte populations during postnatal testis maturation revealed by single-cell sequencing.
Sample Metadata Fields
Age, Disease, Cell line, Subject
View Samples- Mus musculus
- 15 Downloadable Samples
- Illumina HiSeq 2500
Description
Intra-islet crosstalk between islet cells is critical in orchestrating the body’s response to changes in blood glucose levels, but is incompletely understood. In this study, we used transgenic mouse lines that allowed the purification and transcriptomic characterisation of alpha, beta, and delta cells, yielding an RNA-sequencing database that can be searched for regulatory proteins which are differentially expressed between cell types. As an illustrative example, we examined the expression of g-protein coupled receptors, and found that the ghrelin receptor, Ghsr, was highly expressed in delta cells compared to alpha and beta cells. GHSR excitation elicited increases in cytosolic calcium levels in primary delta cells. In the perfused pancreas, the application of ghrelin stimulated somatostatin secretion, correlating with a decrease in insulin and glucagon release, which was sensitive to somatostatin receptor antagonism. These results show that ghrelin acts specifically on delta cells within pancreatic islets to affect blood glucose regulation. Overall design: Examination of transcriptomic profiles obtained from pancreatic alpha, beta and delta cells
Publication Title
Transcriptomic profiling of pancreatic alpha, beta and delta cell populations identifies delta cells as a principal target for ghrelin in mouse islets.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Mus musculus
- 288 Downloadable Samples
- Illumina HiSeq 2500
Description
Enteroendocrine L-cells release hormones that control metabolism and appetite and are targets under investigation for the treatment of diabetes and obesity. Understanding L-cell diversity and expression profiles is critical for identifying target receptors that will translate into altered hormone secretion. We performed single cell RNA sequencing of mouse L-cells from the upper small intestine to distinguish cellular populations, revealing that L-cells form 3 major clusters: a group with typical characteristics of classical L-cells, including high expression of Gcg and Pyy; a cell type overlapping with Gip-expressing K-cells; and a unique cluster expressing Tph1 and Pzp that was predominantly located in duodenal villi and co-produced 5HT. Expression of G-protein coupled receptors differed between clusters, suggesting the cell types are differentially regulated, and would be differentially targetable. Our findings support the emerging concept that many enteroendocrine cell populations are highly overlapping, with individual cells producing a range of peptides previously assigned to distinct cell types. Overall design: Single cell RNA sequencing of mouse duodenal L-cells cells
Publication Title
Single-cell RNA-sequencing reveals a distinct population of proglucagon-expressing cells specific to the mouse upper small intestine.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 127 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The characteristics of immune cells infiltrating pediatric brain tumors is largely unexplored. A better understanding of these characteristics will provide a foundation for development of immunotherapy for pediatric brain tumors.
Publication Title
Characterization of distinct immunophenotypes across pediatric brain tumor types.
Sample Metadata Fields
Specimen part, Disease, Disease stage
View Samples- Homo sapiens
- 104 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
To better understand the pathogenesis of acute promyelocytic leukemia (APL, FAB M3 AML), we identified genes that are expressed differently in APL cells compared to other acute myeloid leukemia subtypes, and to normal promyelocytes. Comparative gene expression analysis of 14 M3, 62 other AML (M0, M1, M2 and M4) and 5 enriched normal promyelocyte samples revealed a signature of 1,121 genes that are specifically dysregulated in M3 samples relative to other AML, and that do not simply represent normal promyelocyte expression (M3-specific signature). We used a novel, high throughput digital platform (Nanostring's nCounter system) to evaluate a subset of the most significantly dysregulated genes in 30 AML samples; 33 of 37 evaluable gene expression patterns were validated. In an additional analysis, we selected only genes that are dysregulated in M3 both compared to other AML subtypes, and to purified normal CD34+ cells, promyelocytes, and/or neutrophils, thereby isolating a 478 gene "composite M3 dysregulome". Surprisingly, the expression of only a few of these genes was significantly altered in PR-9 cells after PML-RARA induction, suggesting that most of these genes are not direct targets of PML-RARA. Comparison of the M3-specific signature to our previously described murine APL dysregulome revealed 33 commonly dysregulated genes, including JUN, EGR1, and TNF. Collectively, these results suggest that PML-RARA initiates a transcriptional cascade which generates a unique downstream expression signature in both primary human and mouse APL cells.
Publication Title
High throughput digital quantification of mRNA abundance in primary human acute myeloid leukemia samples.
Sample Metadata Fields
Sex, Race
View Samples- Bos taurus
- 88 Downloadable Samples
- Affymetrix Bovine Genome Array (bovine)
Description
Establishment of an in vitro system to explore molecular mechanisms of mastitis susceptibility in cattle by comparative expression profiling of Escherichia coli and Staphylococcus aureus inoculated primary cells sampled from cows with different genetic predisposition for somatic cell score
Publication Title
Comparative expression profiling of E. coli and S. aureus inoculated primary mammary gland cells sampled from cows with different genetic predispositions for somatic cell score.
Sample Metadata Fields
Disease, Treatment, Time
View Samples