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GSE99361
Mus musculus
8 Downloadable Samples
Illumina mouseref-8_v2_0_r3 expression beadchip
Description
Informed by the genetic alterations observed in human GBM, we engineered a novel, lentiviral injection mediated, mouse model of proneural GBM.
Publication Title
A recombinant lentiviral PDGF-driven mouse model of proneural glioblastoma.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 10 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
The cellular origin and molecular progression towards aggressive cancers such as acute myeloid leukemia (AML) remain elusive. Clinically, Myelodysplastic syndromes (MDS) and related myeloproliferative neoplasias (MPN) disorders1-5 are believed to present as a precursor stage to lethal AML development. Despite the identification of cytogenetic abnormalities and increased activation of signaling in human MDS/MPN, specific pathways that either sustain or initiate disease progression and evolve into self-sustaining leukemic-initiating cells (L-ICs)13 have not been elucidated. Here we demonstrate that tissue specific loss of glycogen synthase kinase-3 (GSK3 beta) initiates the emergence of stable Pre-leukemic-ICs (PLIC) in vivo. In contrast to deletion or transgenic perturbation of pathways associated with AML eg. -catenin/Wnt, serial transplantation of PL-IC produced abnormal hematological disease that phenotypically and molecularly resembles human MDS/MPN. PL-ICs were exclusively generated from GSK3 beta deficient hematopoietic stem cells (HSCs), indicating that disease initiation events collaborate with existing HSC self-renewal machinery. In the absence of GSK3 beta, subsequent deletion of GSK3 beta caused rapid induction of L-ICs that give rise to lethal AML. As these processes were solely driven by dose-dependent deficiencies in GSK3 beta levels, our results suggest that perturbation of this pathway can sufficiently drive and recapitulate a step-wise progression of disease from HSCs to MDS/MPN and subsequent AML. Our study provides a molecular and cellular foundation to understand AML evolution from pre-leukemic precursors. We suggest that defining the molecular states of pre-neoplastic disease will allow patient stratification at early stages of MDS/MPN onset and aid in the development of therapeutic targeting of causal pathways responsible for the earliest stages of leukemic initiation events.
Publication Title
GSK3 Deficiencies in Hematopoietic Stem Cells Initiate Pre-neoplastic State that Is Predictive of Clinical Outcomes of Human Acute Leukemia.
Sample Metadata Fields
Sex, Specimen part
View Samples- Mus musculus
- 12 Downloadable Samples
Illumina mouseref-8_v2_0_r3 expression beadchip
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
PDGF Engages an E2F-USP1 Signaling Pathway to Support ID2-Mediated Survival of Proneural Glioma Cells.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Mus musculus
- 6 Downloadable Samples
- Illumina mouseref-8_v2_0_r3 expression beadchip
Description
Identification of critical survival determinants of PDGF-driven proneural glioma. Results provided information about the genes and pathways that are regulated by PDGF signaling in PDGF-driven proneural glioma and led to the assessment of the importance of the USP1-ID2 axis in proneural glioma.
Publication Title
PDGF Engages an E2F-USP1 Signaling Pathway to Support ID2-Mediated Survival of Proneural Glioma Cells.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Mus musculus
- 6 Downloadable Samples
- Illumina mouseref-8_v2_0_r3 expression beadchip
Description
Identification of critical survival determinants of PDGF-driven proneural glioma. Results provided information about the genes and pathways that are regulated by PDGF signaling in PDGF-driven proneural glioma and led to the assessment of the importance of the USP1-ID2 axis in proneural glioma.
Publication Title
PDGF Engages an E2F-USP1 Signaling Pathway to Support ID2-Mediated Survival of Proneural Glioma Cells.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 24 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Spleen conventional dendritic cells from NOD mice show a lower overall response to CpG-A compared to B6 cDCs.
Publication Title
Despite Increased Type 1 IFN, Autoimmune Nonobese Diabetic Mice Display Impaired Dendritic Cell Response to CpG and Decreased Nuclear Localization of IFN-Activated STAT1.
Sample Metadata Fields
Sex, Specimen part
View Samples- Drosophila melanogaster
- 4 Downloadable Samples
- Affymetrix Drosophila Genome Array (drosgenome1)
Description
Effect of injury and Pseudomonas aeruginosa inoculation in Drosophila melanogaster
Publication Title
Involvement of skeletal muscle gene regulatory network in susceptibility to wound infection following trauma.
Sample Metadata Fields
Sex, Time
View Samples- Pseudomonas aeruginosa
- 10 Downloadable Samples
- Affymetrix Pseudomonas aeruginosa Array (paeg1a)
Description
The Pseudomonas aeruginosa MvfR-dependent QS regulatory pathway controls the expression of key virulence genes; and is activated via the extracellular signals 4-hydroxy-2-heptylquinoline (HHQ) and 3,4-dihydroxy-2-heptylquinoline (PQS), whose syntheses depend on anthranilic acid (AA), the primary precursor of 4-hydroxy-2-alkylquinolines (HAQs). We identified halogenated AA analogs that specifically inhibited HAQ biosynthesis and disrupted MvfR-dependent gene expression. These compounds restricted P. aeruginosa systemic dissemination and mortality in mice, without perturbing bacterial viability, and inhibited osmoprotection, a widespread bacterial function.
Publication Title
Inhibitors of pathogen intercellular signals as selective anti-infective compounds.
Sample Metadata Fields
No sample metadata fields
View Samples- Arabidopsis thaliana
- 7 Downloadable Samples
- Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)
Description
Global analysis of brassinosteroid (BR)-mediated gene expression under abiotic stress identifies BR associated mechanisms of stress tolerance, and new stress-related genes
Publication Title
Gene expression and functional analyses in brassinosteroid-mediated stress tolerance.
Sample Metadata Fields
Age, Specimen part
View Samples- Mus musculus, Homo sapiens
- 8 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Identification of distinct changes in gene expression after modulation of melanoma tumor antigen p97 (melanotransferrin) in multiple models in vitro and in vivo.
Sample Metadata Fields
Cell line
View Samples