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GSE12870
Homo sapiens
36 Downloadable Samples
Sentrix Human-6 Expression BeadChip
Description
There is emerging evidence that, beyond their cholesterol lowering properties, statins exhibit important antileukemic effects in vitro and in vivo, but the precise mechanisms by which they generate such responses remain to be determined. We have previously shown that statins promote differentiation of acute promyelocytic leukemia (APL) cells and enhance generation of all-trans-retinoic acid (ATRA)-dependent antileukemic responses. We now provide evidence that statin-dependent leukemic cell differentiation requires engagement and activation of the JNK kinase pathway. In addition, in experiments to define the molecular targets and mediators of statin-induced differentiation we found a remarkable effect of statins on ATRA-dependent gene transcription, evidenced by the selective induction of over 400 genes by the combination of atorvastatin and ATRA. Altogether, our studies identify novel statin molecular targets linked to differentiation, establish that statins modulate ATRA-dependent transcription, and suggest that combined use of statins with retinoids may provide a novel approach to enhance antileukemic responses in APL and possibly other leukemias.
Publication Title
Regulation of leukemic cell differentiation and retinoid-induced gene expression by statins.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 4 Downloadable Samples
- Affymetrix Mouse Genome 430A 2.0 Array (mouse430a2)
Description
Dendritic cells are the sentinels of the innate immune system. We used global microarray analysis to identify genes which are regulated by Toll-like receptor signaling pathways.
Publication Title
IRF8 directs stress-induced autophagy in macrophages and promotes clearance of Listeria monocytogenes.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Mus musculus
- 18 Downloadable Samples
Illumina HiSeq 2500
Description
Host defense by the innate immune system requires the establishment of antimicrobial states allowing cells to cope with microorganisms before the onset of the adaptive immune response. Interferons (IFN) are of vital importance in the establishment of cell-autonomous antimicrobial immunity. Speed is therefore an important attribute of the cellular response to IFN. With much of the antimicrobial response being installed de novo, this pertains foremost to gene expression, the rapid switch between resting-state and active-state transcription of host defense genes. Our results show how mRNA expression changes upon IFNb or IFNg treatment in wild typ and Irf9-/- bone marrow derived macrophages. Overall design: Methods: Bone marrow derived macrophage mRNA of wild-type (WT) and Irf9 knock out mice (IRF9-/-) untreated, as well as 2h IFNb and IFNg treated were generated by deep sequencing, in triplicate, using Illumina sequencing.
Publication Title
A molecular switch from STAT2-IRF9 to ISGF3 underlies interferon-induced gene transcription.
Sample Metadata Fields
Specimen part, Cell line, Treatment, Subject
View Samples- Mus musculus
- 12 Downloadable Samples
- Illumina HiSeq 2500
Description
Host defense by the innate immune system requires the establishment of antimicrobial states allowing cells to cope with microorganisms before the onset of the adaptive immune response. Interferons (IFN) are of vital importance in the establishment of cell-autonomous antimicrobial immunity. Speed is therefore an important attribute of the cellular response to IFN. With much of the antimicrobial response being installed de novo, this pertains foremost to gene expression, the rapid switch between resting-state and active-state transcription of host defense genes. Our results show how mRNA expression changes upon IFNb treatment in wild type and Irf9-/- mouse embryonic fibroblasts. Overall design: Methods: Mouse embryonic fibroblast (MEF) mRNA of wild-type (WT) and Irf9 knock out mice (IRF9-/-) untreated, as well as 2h IFNb treated were generated by deep sequencing, in triplicate, using Illumina sequencing.
Publication Title
A molecular switch from STAT2-IRF9 to ISGF3 underlies interferon-induced gene transcription.
Sample Metadata Fields
Subject
View Samples- Homo sapiens
- 12 Downloadable Samples
- Illumina HiSeq 2500
Description
Host defense by the innate immune system requires the establishment of antimicrobial states allowing cells to cope with microorganisms before the onset of the adaptive immune response. Interferons (IFN) are of vital importance in the establishment of cell-autonomous antimicrobial immunity. Speed is therefore an important attribute of the cellular response to IFN. With much of the antimicrobial response being installed de novo, this pertains foremost to gene expression, the rapid switch between resting-state and active-state transcription of host defense genes. Our results show how mRNA expression changes upon IFNb treatment in wild type and Irf9-/- THP1 cells. Overall design: Methods: mRNA of untreated and IFNb treated wild-type (WT) and Irf9 knock out (IRF9-/-) human monocytic THP1 cells were analyzed by deep sequencing, in triplicate, using Illumina sequencing.
Publication Title
A molecular switch from STAT2-IRF9 to ISGF3 underlies interferon-induced gene transcription.
Sample Metadata Fields
Subject
View Samples- Homo sapiens
- 12 Downloadable Samples
- Illumina HiSeq 2000
Description
There is some emerging evidence that members of the Schlafen (SLFN) family of proteins mediate antineoplastic responses, but the mechanisms accounting for these effects are not known. We provide evidence that human SLFN5, an interferon (IFN)- inducible member of the family, exhibits key roles in controlling motility and invasiveness of renal cell carcinoma (RCC) cells. Our studies define the mechanism by which this occurs, demonstrating that SLFN5 negatively controls expression of matrix metalloproteinases (MMP)-1 and -13 and several other genes involved in the control of malignant cell motility. Importantly, our data establish that SLFN5 expression correlates with a better overall survival in a large cohort of patients with RCC. The inverse relationship between SLFN5 expression and RCC aggressiveness raises the possibility of developing unique therapeutic approaches in the treatment of RCC, by modulating SLFN5 expression. Overall design: Examination of 2 SLFN5 knockdown cells and 2 controls, in triplicate.
Publication Title
Human Schlafen 5 (SLFN5) Is a Regulator of Motility and Invasiveness of Renal Cell Carcinoma Cells.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 18 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Wnt signaling is intrinsic to mouse embryonic stem cell self-renewal. Therefore it is surprising that reprogramming of somatic cells to induced pluripotent stem cells (iPSCs) is not strongly enhanced by Wnt signaling. Here, we demonstrate that active Wnt signaling inhibits the early stage of reprogramming to iPSCs, while it is required and even stimulating during the late stage. Mechanistically, this biphasic effect of Wnt signaling is accompanied by a change in the requirement of all four of its transcriptional effectors: Tcf1, Lef1, Tcf3, and Tcf4. For example, Tcf3 and Tcf4 are stimulatory early but inhibitory late in the reprogramming process. Accordingly, ectopic expression of Tcf3 early in reprogramming combined with its loss-of-function late enables efficient reprogramming in the absence of ectopic Sox2. Together, our data indicate that the step-wise process of reprogramming to iPSCs is critically dependent on the stage-specific control and action of all four Tcfs and Wnt signaling.
Publication Title
Stage-specific regulation of reprogramming to induced pluripotent stem cells by Wnt signaling and T cell factor proteins.
Sample Metadata Fields
Specimen part, Time
View Samples- Homo sapiens
- 9 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Detailed analysis comparing hiPSC lines that were newly generated and compared them to already established hiPSC lines
Publication Title
Molecular analyses of human induced pluripotent stem cells and embryonic stem cells.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Mus musculus
- 16 Downloadable Samples
- Illumina HiSeq 2000
Description
Bone marrow derived macrophages were infected with Listeria monocytogenes for 4 hours. We investigated differently expressed genes in the absence of DDX3X upon infection and also in steady state conditions. Overall design: Investigation of gene expression in wt and Ddx3x deficient bone marrow derived macrophages in response to Listeria monocytogenes infection.
Publication Title
The RNA helicase DDX3X is an essential mediator of innate antimicrobial immunity.
Sample Metadata Fields
Sex, Specimen part, Subject
View Samples- Homo sapiens
- 46 Downloadable Samples
- Illumina humanRef-8 v2.0 expression beadchip
Description
Numerous studies have shown the potential of spermatozoal RNAs to delineate failures of spermatogenic pathways in infertile samples. However, the RNA contribution of normal fertile samples still needs to be established in relation to transcripts consistently present in human spermatozoa. We report here the spermatozoal transcript profiles characteristic of 24 normally fertile individuals. RNA was extracted from the purified sperm cells of ejaculate and hybridized to Illumina Human-8 BeadChip Microarrays
Publication Title
Identification of human sperm transcripts as candidate markers of male fertility.
Sample Metadata Fields
No sample metadata fields
View Samples