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GSE144826
Homo sapiens
878 Downloadable Samples
Affymetrix Human Gene 2.1 ST Array (hugene21st)
Description
Identifying immune correlates of protection and mechanisms of immunity accelerates and streamlines the development of vaccines. RTS,S/AS01E, the most advanced malaria vaccine, has moderate efficacy in African children. In contrast, immunization with sporozoites under antimalarial chemoprophylaxis (CPS immunization) can provide 100% sterile protection in naïve adults. We used systems biology approaches to identify correlates of vaccine-induced immunity based on transcriptomes of peripheral blood mononuclear cells from subjects immunized with RTS,S/AS01E or chemo-attenuated sporozoites stimulated with parasite antigens in vitro. Specifically, we used samples of subjects from two age cohorts and 3 African countries participating in an RTS,S/AS01E pediatric phase 3 trial and malaria-naïve subjects participating in a CPS trial. We identified both pre-immunization and post-immunization transcriptomic signatures correlating with protection. Signatures were validated in independent children and infants from the RTS,S/AS01E phase 3 trial and subjects from an independent CPS trial with high accuracies (>70%). Transcription modules revealed interferon, NF-B, TLR, and monocyte-related signatures associated with protection. Pre-immunization signatures suggest the potential for strategies to prime the immune system before vaccination towards improving vaccine immunogenicity and efficacy. Finally, signatures of protection could be useful to determine efficacy in clinical trials, accelerating vaccine candidate testing. Nevertheless, signatures should be tested more extensively across multiple cohorts and trials to demonstrate their universal predictive capacity.
Publication Title
Antigen-stimulated PBMC transcriptional protective signatures for malaria immunization.
Sample Metadata Fields
Sex, Specimen part, Subject, Time
View Samples- Homo sapiens
- 12 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Recurrent 8q24 rearrangement in blastic plasmacytoid dendritic cell neoplasm: association with immunoblastoid cytomorphology, MYC expression, and drug response.
Sample Metadata Fields
Specimen part, Disease, Disease stage, Cell line
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare skin-tropic hematological malignancy of uncertain pathogenesis and poor prognosis. We examined 118 BPDCN cases for cytomorphology, MYC locus rearrangement, and MYC expression. Sixty-two (53%) and 41 (35%) showed the classic and immunoblastoid cytomorphology, respectively. Forty-one (38%) MYC+BPDCN (positive for rearrangement and expression) and 59 (54%) MYC-BPDCN (both negative) cases were identified. Immunoblastoid cytomorphology was significantly associated with MYC+BPDCN. All examined MYC+BPDCNs were negative for MYB/MYBL1 rearrangement (0/36). Clinically, MYC+BPDCN showed older onset, poorer outcome, and localized skin tumors more commonly than MYC-BPDCN. MYC was demonstrated by expression profiling as one of the clearest discriminators between CAL-1 (MYC+BPDCN) and PMDC05 (MYC-BPDCN) cell lines, and its shRNA knockdown suppressed CAL-1 viability. Inhibitors for bromodomain and extraterminal protein (BETis) and aurora kinases (AKis) inhibited CAL-1 growth more effectively than PMDC05. We further showed that a BCL2 inhibitor was effective in both CAL-1 and PMDC05, indicating that this inhibitor can be used to treat MYC-BPDCN, to which BETis and AKis are probably less effective. Our data will provide a rationale for the development of new treatment strategies for patients with BPDCN in accordance with precision medicine.
Publication Title
Recurrent 8q24 rearrangement in blastic plasmacytoid dendritic cell neoplasm: association with immunoblastoid cytomorphology, MYC expression, and drug response.
Sample Metadata Fields
Specimen part, Disease, Disease stage, Cell line
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare skin-tropic hematological malignancy of uncertain pathogenesis and poor prognosis. We examined 118 BPDCN cases for cytomorphology, MYC locus rearrangement, and MYC expression. Sixty-two (53%) and 41 (35%) showed the classic and immunoblastoid cytomorphology, respectively. Forty-one (38%) MYC+BPDCN (positive for rearrangement and expression) and 59 (54%) MYC-BPDCN (both negative) cases were identified. Immunoblastoid cytomorphology was significantly associated with MYC+BPDCN. All examined MYC+BPDCNs were negative for MYB/MYBL1 rearrangement (0/36). Clinically, MYC+BPDCN showed older onset, poorer outcome, and localized skin tumors more commonly than MYC-BPDCN. MYC was demonstrated by expression profiling as one of the clearest discriminators between CAL-1 (MYC+BPDCN) and PMDC05 (MYC-BPDCN) cell lines, and its shRNA knockdown suppressed CAL-1 viability. Inhibitors for bromodomain and extraterminal protein (BETis) and aurora kinases (AKis) inhibited CAL-1 growth more effectively than PMDC05. We further showed that a BCL2 inhibitor was effective in both CAL-1 and PMDC05, indicating that this inhibitor can be used to treat MYC-BPDCN, to which BETis and AKis are probably less effective. Our data will provide a rationale for the development of new treatment strategies for patients with BPDCN in accordance with precision medicine.
Publication Title
Recurrent 8q24 rearrangement in blastic plasmacytoid dendritic cell neoplasm: association with immunoblastoid cytomorphology, MYC expression, and drug response.
Sample Metadata Fields
Specimen part, Disease, Disease stage, Cell line
View Samples- Drosophila melanogaster
- 78 Downloadable Samples
Illumina Genome Analyzer IIx, Illumina HiSeq 2000
Description
Purpose: We isolated Drosophila midgut cells : Delta+ intestinal stem cells (ISCs), Su(H)+enteroblasts (EBs), Esg+ cells (ISC+EB), Myo1A+Enterocytes (ECs), Pros+Enteroendocrine cells (EEs) and How+Visceral muscle cells (VM) from whole midguts to identify stem cell specific genes and study cell type specificities of midgut cells. We also isolated all the cell types from the 5 major regions (R1-R5) of the Drosophila midgut to study differences in cells in different regions. Methods: 3-7 day old female flies were dissected. Flies with GFP/YFP marking different cell types (using the GAL4-UAS system) were used to separate cells of the midgut.The midguts were dissociated with Elastase and FACS sorted using FACS AriaIII. RNA was extracted, amplified and sequenced. Whole midgut samples were sequenced on Illumina GAIIX and regional cell populations were sequenced on HiSeq2000. Methods:Raw fastqc reads were mapped to the Drosophila genome (Drosophila_melanogaster.BDGP5.70.dna.toplevel.fa) using Tophat 2.0.9 at default (using boost_1_54_0, bowtie2-2.1.0, samtools-0.1.19). Methods: For differential expression analysis, DESeq (p-value adjustment 0.05 by method Benjamini-Hochberg) was used. The reads were normalized also to Reads per kilobase of transcript per million mapped reads (RPKM). Results: More than 50% of the genome is expressed in the adult midgut (FlyAtlas- Chintapalli et al., 2007), of these genes about 50% (2457) were differentially expressed (DE) between all 4 cell types (ISCs, EBs, ECs and EEs) atleast 2 folds with 95% confidence Results: 159 genes that were specifically enriched in ISCs, 509 genes were specifically repressed in ISCs Conclusions: Our study represents the first detailed analysis of Drosophila intestinal cell transcriptomes, with biologic replicates, generated by RNA-seq technology.Our data facilitates comparative investigations of expression profiles of cells and reveals novel stem cell genes. Further region specific profiling adds precision to the analysis of variances in the midgut regions. We identify transcriptional regulators and regional transcription factors which modulate the midgut physiology. The dataset will be a great resource for hypothesis generation, tool building and fine tuned studies on the Drosophila midgut. Overall design: mRNA profiles of Drosophila intestinal cells from whole midguts and midgut regions were generated by Deep Sequencing. Whole midgut profiles were generated in triplicates (Illumina GAIIx, 72 bp read length) and regional cell type profiles were genrated in duplicates (HiSeq 2000, 50bp read length).
Publication Title
Regional Cell-Specific Transcriptome Mapping Reveals Regulatory Complexity in the Adult Drosophila Midgut.
Sample Metadata Fields
Sex, Specimen part, Subject
View Samples- Homo sapiens
- 41 Downloadable Samples
- Illumina human-6 v2.0 expression beadchip
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Retinoic acid-induced pancreatic stellate cell quiescence reduces paracrine Wnt-β-catenin signaling to slow tumor progression.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 30 Downloadable Samples
- Illumina human-6 v2.0 expression beadchip
Description
We evaluated the change in expression of genes after treatment of stellate cells with retinoic acid to understand how the stellate cells can de-differentiate and effect their physiological behaviour in pathological conditions. We then tested the changes in the gene expression in 2D and 3D culture conditions for pancreatic stellate cells and in a pancreatic cancer model.
Publication Title
Retinoic acid-induced pancreatic stellate cell quiescence reduces paracrine Wnt-β-catenin signaling to slow tumor progression.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 9 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Genomic occupancy of Runx2 with global expression profiling identifies a novel dimension to control of osteoblastogenesis.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 11 Downloadable Samples
- Illumina human-6 v2.0 expression beadchip
Description
We evaluated the change in expression of genes after treatment of stellate cells with retinoic acid to understand how the stellate cells can de-differentiate and effect their physiological behaviour in pathological conditions. We then tested the changes in the gene expression in 2D and 3D culture conditions for pancreatic stellate cells and in a pancreatic cancer model.
Publication Title
Retinoic acid-induced pancreatic stellate cell quiescence reduces paracrine Wnt-β-catenin signaling to slow tumor progression.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 9 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Osteogenesis is a highly regulated developmental process and continues during the turnover and repair of mature bone. Runx2, the master regulator of osteoblastogenesis, directs a transcription program essential for bone formation through both genetic and epigenetic mechanisms. While individual Runx2 gene targets have been identified, further insights into the broad spectrum of Runx2 functions required for osteogenesis are needed. By performing genome-wide characterization of Runx2 binding at the three major stages of osteoblast differentiation: proliferation, matrix deposition and mineralization, we identified Runx2-dependent regulatory networks driving bone formation. Using chromatin immunoprecipitation followed by high-throughput sequencing (ChIP-Seq) over the course of these stages, we discovered close to 80,000 significantly enriched regions of Runx2 binding throughout the mouse genome. These binding events exhibited distinct patterns during osteogenesis, and were associated with proximal promoters as well as a large percentage of Runx2 occupancy in non-promoter regions: upstream, introns, exons, transcription termination site (TTS) regions, and intergenic regions. These peaks were partitioned into clusters that are associated with genes in complex biological processes that support bone formation. Using Affymetrix expression profiling of differentiating osteoblasts depleted of Runx2, we identified novel Runx2 targets including Ezh2, a critical epigenetic regulator; Crabp2, a retinoic acid signaling component; Adamts4 and Tnfrsf19, two remodelers of extracellular matrix. We demonstrated by luciferase assays that these novel biological targets are regulated by Runx2 occupancy at non-promoter regions. Our data establish that Runx2 interactions with chromatin across the genome reveal novel genes, pathways and transcriptional mechanisms that contribute to the regulation of osteoblastogenesis.
Publication Title
Genomic occupancy of Runx2 with global expression profiling identifies a novel dimension to control of osteoblastogenesis.
Sample Metadata Fields
Specimen part
View Samples