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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- Mus musculus, Homo sapiens
- 62 Downloadable Samples
Affymetrix Human Gene 2.0 ST Array (hugene20st), Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Stem cell-derived tissues have wide potential for modelling developmental and pathological processes as well as cell-based therapy. However, it has proven difficult to generate several key cell types in vitro, including skeletal muscle. In vertebrates, skeletal muscles derive during embryogenesis from the presomitic mesoderm (PSM). Using PSM development as a guide to establish conditions for the differentiation of monolayer cultures of embryonic stem (ES) cells into PSM-like cells without the introduction of transgenes or cell sorting.
Publication Title
A Gradient of Glycolytic Activity Coordinates FGF and Wnt Signaling during Elongation of the Body Axis in Amniote Embryos.
Sample Metadata Fields
Specimen part, Disease, Cell line, Treatment, Time
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Original patient tumor is directly implanted in mice xenografts. Tumor is propagated to multiple mice for conduct of 6 arm treatment trials and control. Therapies are selected based on T0 and F0 genomic profiles.
Publication Title
Using a rhabdomyosarcoma patient-derived xenograft to examine precision medicine approaches and model acquired resistance.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 32 Downloadable Samples
Illumina Genome Analyzer
Description
Uterine double conditional inactivation of Smad2 and Smad3 in mice results in endometrial dysregulation, infertility, and uterine cancer. Smad2/3 cKO mice demonstrate abnormal expression of genes involved in inflammation, cell-cycle checkpoint, migration, steroid biosynthesis, and SMAD1/5-driven genes. We performed RNA-sequencing to identify the gene expression differences between the uterine epithelium of control and Smad2/3 cKO. To control for estrous cycle variations, the uterine epithelium was collected from mice at 0.5 dpc. Global gene expression profiles of Smad2/3 cKO versus control mice was analyzed. Our RNA sequencing analysis was performed at 6 weeks of life and already showed significant differences in migratory (Agr2,Slit2) and inflammatory (Ccl20, Crispld2) markers between Smad2/3 cKO and control mice. Overall design: Two group comparison: uterine epithelium of control and Smad2/3 cKO mice. We generated a conditional knockout of Smad2/3 in the uterus and demonstrated that Smad2/3 plays a critical role in the endometrium, with disruption resulting in pubertal-onset uterine hyperplasia and ultimately fatal uterine cancer.
Publication Title
Uterine double-conditional inactivation of <i>Smad2</i> and <i>Smad3</i> in mice causes endometrial dysregulation, infertility, and uterine cancer.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 9 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Glioblastoma multiforme (GBM) is the most malignant and most common tumor of the central nervous system characterized by rapid growth and extensive tissue infiltration. GBM results in more years of life lost than any other cancer type. Notch signaling has been implicated in GBM pathogenesis through several modes of action. Inhibition of Notch leads to a reduction of cancer-initiating cells in gliomas and reduces proliferation and migration. Deltex1 (DTX1) is part of an alternative Notch signaling pathway distinct from the canonical MAML1/RBPJ-mediated cascade. In this study, we show that DTX1 activates both the RTK/PI3K/PKB as well as the MAPK/ERK pathway. Moreover, we found the anti-apoptotic factor Mcl-1 to be induced by DTX1. In accordance with this, the clonogenic potential and proliferation rates of glioma cell lines correlated with DTX1 levels. DTX1 knock down mitigated the tumorigenic potential in vivo, and overexpression of DTX1 increased cell migration and invasion of tumor cells accompanied by an elevation of the pro-migratory factors PKB and Snail1. Microarray gene expression analysis identified a DTX1-specific transcriptional program - including microRNA-21 - which is distinct from the canonical Notch signaling. We propose the alternative Notch pathway via DTX1 as oncogenic factor in malignant glioma and found low DTX1 expression levels to correlate with prolonged survival of GBM and early breast cancer patients in open source databases.
Publication Title
Deltex-1 activates mitotic signaling and proliferation and increases the clonogenic and invasive potential of U373 and LN18 glioblastoma cells and correlates with patient survival.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Mus musculus
- 11 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Posterior embryonic axis develops from neuromesodermal progenitors which differentiate into neural tube and paraxial mesoderm
Publication Title
Recapitulating early development of mouse musculoskeletal precursors of the paraxial mesoderm <i>in vitro</i>.
Sample Metadata Fields
Treatment
View Samples- Homo sapiens
- 9 Downloadable Samples
- Affymetrix Human Gene 2.0 ST Array (hugene20st), Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Stem cell-derived tissues have wide potential for modelling developmental and pathological processes as well as cell-based therapy. However, it has proven difficult to generate several key cell types in vitro, including skeletal muscle. In vertebrates, skeletal muscles derive during embryogenesis from the presomitic mesoderm (PSM). Using PSM development as a guide, we establish conditions for the differentiation of monolayer cultures of human pluripotent stem (hPSC) cells into PSM-like cells without the introduction of transgenes or cell sorting. We differentiated human PSCs in serum-free medium supplemented with Chir99021 only (C medium) or with also the Bmp inhibitor LDN193189 (CL medium). In vivo, the PSM cells are first expressing MSGN1 (posterior PSM marker) and then mature to express Pax3 (anterior PSM marker). After 4-5 days of differentiation of hPSCs, MSGN1-positive cells were FACS-sorted and their transcriptome analyzed.
Publication Title
Recapitulating early development of mouse musculoskeletal precursors of the paraxial mesoderm <i>in vitro</i>.
Sample Metadata Fields
Treatment
View Samples- Mus musculus
- 18 Downloadable Samples
- Illumina MouseWG-6 v2.0 expression beadchip
Description
By utilizing mast cells lacking Dnmt3a, we found that this enzyme is involved in restraining mast cell responses to stimuli, both in vitro and in vivo.
Publication Title
<i>Dnmt3a</i> restrains mast cell inflammatory responses.
Sample Metadata Fields
Sex, Specimen part, Treatment
View Samples- Mus musculus
- 16 Downloadable Samples
- Affymetrix Murine Genome U74A Version 2 Array (mgu74av2)
Description
In order to establish a list of candidate direct COUP-TFI gene targets in the inner ear, we analyzed the differential gene expression profiles of the wild-type and the COUP-TFI/ P0 inner ears.
Publication Title
Genome-wide analysis of binding sites and direct target genes of the orphan nuclear receptor NR2F1/COUP-TFI.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 41 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
To identify signaling pathways that are differentially regulated in human gliomas, a microarray analysis on 30 brain tumor samples (12 primary glioblastomas (GBM), 3 secondary glioblastomas (GBM-2), 8 astrocytomas (Astro) and 7 oligodendrogliomas (Oligo)) and on 5 glioblastoma cell lines (LN018, LN215, LN229, LN319 and BS149) was performed. Normal brain tissue (NB) and normal human astrocytes (NHA) were used as a control. Kinase expression in each tumor was compared to expression in normal brain and expression values from normal human astrocytes were used as an additional control.
Publication Title
MAP kinase-interacting kinase 1 regulates SMAD2-dependent TGF-β signaling pathway in human glioblastoma.
Sample Metadata Fields
Sex, Age, Specimen part, Disease stage, Cell line
View Samples