Filters
Technology
Platform
GSE57864
Homo sapiens
11 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Both diploid RPE-1 and BJ-1 cells were made tetraploid by transient treatment with the cytokinesis inhibitor DCD. Proliferating tetraploids from both BJ-1 and RPE-1 were selected and isolated. The gene expression profiles of the proliferating tetraploid cells were then compared to the diploids from which they originated.
Publication Title
Cytokinesis failure triggers hippo tumor suppressor pathway activation.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Genome 430A 2.0 Array (mouse430a2)
Description
Genetically unstable tetraploid cells can promote tumorigenesis. Recent estimates suggest that ~37% of human tumors have undergone a genome-doubling event during their development. This potentially oncogenic effect of tetraploidy is countered by a p53-dependent barrier to proliferation. However, the cellular defects and corresponding signaling pathways that trigger growth suppression in tetraploid cells are not known. Here we combine genome-scale RNAi screening and in vitro evolution approaches to demonstrate that cytokinesis failure activates the Hippo tumor suppressor pathway in cultured cells as well as in naturally occurring tetraploid cells in vivo. Induction of the Hippo pathway is triggered in part by extra centrosomes, which alter small G-protein signaling and activate LATS2 kinase; LATS2 in turn stabilizes p53 and inhibits the transcriptional regulators YAP and TAZ. These findings define an important tumor suppression mechanism. Furthermore, our experiments uncover adaptations that allow nascent tumor cells to bypass this inhibitory regulation.
Publication Title
Cytokinesis failure triggers hippo tumor suppressor pathway activation.
Sample Metadata Fields
Age, Specimen part
View Samples- Mus musculus
- 18 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Hippo pathway activity influences liver cell fate.
Sample Metadata Fields
Specimen part, Time
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Hippo signaling is highly associated with activity in the stem cell compartment of many epithelial tissues. In this study, we examined if Hippo signaling inhibition (by inducing Yap expression) could convert differentiated cells into a progenitor like phenotype. Organoid cells derived from mouse livers under various conditions, wild-type, Yap ON (Plus Dox), and Yap ON then OFF (Minus Dox) was examined.
Publication Title
Hippo pathway activity influences liver cell fate.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Hippo signaling is highly associated with activity in the stem cell compartment of many epithelial tissues. In this study, we examined if Hippo signaling inhibition (by inducing Yap expression) could convert differentiated cells into a progenitor like phenotype.
Publication Title
Hippo pathway activity influences liver cell fate.
Sample Metadata Fields
Specimen part, Time
View Samples- Homo sapiens
- 3 Downloadable Samples
Illumina Genome Analyzer IIx
Description
We aimed to identify microRNAs that are regulated by YAP in human mammary epithelial cells. Overall design: We utilized deep sequencing technology to identify microRNAs that are induced by YAP overexpression and repressed by YAP knockdown.
Publication Title
YAP mediates crosstalk between the Hippo and PI(3)K–TOR pathways by suppressing PTEN via miR-29.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Mus musculus
- 9 Downloadable Samples
- Illumina HiSeq 1500
Description
Purpose:This work aimed to identify the genetic profiles of piriform projection neurons and characterize their spatial organization within the piriform cortex. Methods: We microdissected the three layers of pirifrom cortex by laser capture (LMD) and performed RNA deep sequencing in order to identify layer-specific molecular markers, we then validated these data by using RNA in situ hybridization and immunohistochemistry.We next performed anterograde neural tracing experiments to identify piriform target regions, and retrograde neural tracing experiments to analyze how piriform projection neurons are organized within piriform cortex.We then combined the analysis of patterns of gene expression with retrograde tracing experiments to identify molecular signatures of the different subclasses of piriform projecting neurons. Results:We show that layers and sub-layers of the piriform cortex can be discriminated by gene expression patterns in adult piriform cortex. We observe that neurons projecting to distinct target areas are localized in distinct layers and express specific genes. We demonstrate that these molecular signatures of piriform projection neurons are maintained in reeler mice, in which cortical lamination is lost and neural positioning is scrambled, suggesting that piriform output connectivity strictly depends on the molecular programm, rather than a proper lamination of the cortex. Conclusion:These results provide important insights into the principles underling the piriform connectivity. Overall design: 3 replicates per each layer (three layers) of piriform cotrex were used for the RNA deep sequancing
Publication Title
Molecular signatures of neural connectivity in the olfactory cortex.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Gene 2.0 ST Array (mogene20st)
Description
CD4+ T cell differentiation into multiple T helper lineages is critical for optimal adaptive immune responses. This report identified a novel intrinsic mechanism by which PD-1 signaling imparted regulatory phenotype to FoxP3+ Th1 cells (denoted as Tbet+iTregPDL1 cells) and iTregs. Tbet+iTregPDL1 cells were capable of preventing inflammation in murine models of experimental colitis and experimental graft versus host disease. PDL-1 binding to PD-1 imparted regulatory function to Tbet+iTregPDL1 cells and iTregs by specifically downregulating an endolysosomal protease asparaginyl endopeptidase (AEP)
Publication Title
PD-1 Inhibitory Receptor Downregulates Asparaginyl Endopeptidase and Maintains Foxp3 Transcription Factor Stability in Induced Regulatory T Cells.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 12 Downloadable Samples
- Illumina HiSeq 2500
Description
In acute myeloid leukemia, chemotherapy resistance remains prevalent and poorly understood. Using functional proteomics of patient AML specimens, we identified MEF2C S222 phosphorylation as a specific marker of primary chemoresistance. We found that transgenic Mef2cS222A/S222A mice engineered to block MEF2C phosphorylation exhibited normal hematopoiesis, but were resistant to leukemogenesis induced by MLL-AF9. MEF2C phosphorylation was required for leukemia stem cell maintenance, induced by MARK kinases in cells, and blocked by selective MARK inhibitor MRT199665, which caused apoptosis of MEF2C-activated human AML cell lines and primary patient specimens, but not those lacking MEF2C. These findings identify signaling-dependent dysregulation of transcription factor control as a determinant of therapy response in AML, with immediate potential for improved diagnosis and therapy for this disease. Overall design: RNA-sequencing of human leukemia cell line with induction of wildtype or mutant MEF2C.
Publication Title
MEF2C Phosphorylation Is Required for Chemotherapy Resistance in Acute Myeloid Leukemia.
Sample Metadata Fields
Specimen part, Cell line, Treatment, Subject
View Samples- Homo sapiens
- 6 Downloadable Samples
- Illumina HiSeq 2500
Description
In acute myeloid leukemia, chemotherapy resistance remains prevalent and poorly understood. Using functional proteomics of patient AML specimens, we identified MEF2C S222 phosphorylation as a specific marker of primary chemoresistance. We found that transgenic Mef2cS222A/S222A mice engineered to block MEF2C phosphorylation exhibited normal hematopoiesis, but were resistant to leukemogenesis induced by MLL-AF9. MEF2C phosphorylation was required for leukemia stem cell maintenance, induced by MARK kinases in cells, and blocked by selective MARK inhibitor MRT199665, which caused apoptosis of MEF2C-activated human AML cell lines and primary patient specimens, but not those lacking MEF2C. These findings identify signaling-dependent dysregulation of transcription factor control as a determinant of therapy response in AML, with immediate potential for improved diagnosis and therapy for this disease. Overall design: RNA-sequencing of human leukemia cell line with treatment of MARK inhibitor MRT199665.
Publication Title
MEF2C Phosphorylation Is Required for Chemotherapy Resistance in Acute Myeloid Leukemia.
Sample Metadata Fields
Specimen part, Cell line, Treatment, Subject
View Samples