Expression data from E18 mouse dorsal telencephalon
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE58727 | GEO | 2014/07/29
SECONDARY ACCESSION(S): PRJNA253281
REPOSITORIES: GEO
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Project description:Radial progenitors deficient in both Mek1 and Mek2 fail to transition to the gliogenic mode in late embryogenesis, and astrocyte and oligodendroglial precursors fail to appear. In exploring mechanisms, we found the Ets transcription family member Etv5/Erm is strongly regulated by MEK. Our microarray assay showed that Erm is specifically downregulated in Mek mutant brain. RNA was extracted from dorsal corticies of E18.5 WT or Mek1,2\NesCre conditional mutant embryos. There were totally 4 samples: 2 WT and 2 mutants. 200 ng of total RNA was prepared for microarray hybridization according to the GeneChip® Whole Transcript (WT) Sense Target Labeling Assay user manual.
2012-09-06 | E-GEOD-40675 | biostudies-arrayexpress
Project description:The two vertebrate Gsk-3 isoforms, Gsk-3a and Gsk-3b, are encoded by distinct genetic loci and exhibit mostly redundant function in murine embryonic stem cells (ESCs). Here we report that deletion of both Gsk-3a and Gsk-3b in mouse ESCs results in significant changes in gene expression. In contrast, deletion of either Gsk-3a or Gsk-3b individually had little effect on gene expression. These data support the notion that Gsk-3 isoforms are functionally redundant in embryonic stem cells. In addition, we did not find the expected upregulation of known Wnt target genes. Our data suggests that Gsk-3-meidated regulation of gene expression in embryonic stem cells is complex, and likely involves affects on numerous signaling pathways. The study was designed to examine the changes in gene expression between wild-type, Gsk-3a-/-, Gsk-3b-/-, and Gsk-3a-/-;Gsk-3b-/- mouse embryonic stem cells.
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Project description:GSK-3b plays a critical role in regulating the Wnt/b-catenin signaling pathway, and manipulating GSK-3b in dendritic cells (DCs) has been shown to improve anti-tumor efficacy of DC vaccines. Since inhibition of GSK-3b leads to activation of b-catenin, we hypothesize that blocking GSK-3b in DCs negatively regulates DC-mediated CD8 T cell immunity and anti-tumor immunity. Using CD11c-GSK-3b-/- conditional knockout mice in which GSK-3b is genetically deleted in CD11c-expressing DCs, we surprisingly found that deletion of GSK-3b in DCs resulted in increased anti-tumor immunity, which contradicted our initial expectation of reduced anti-tumor immunity due to presumed upregulation of b-catenin in DCs. Indeed, we found by both western blot and flow cytometry that deletion of GSK-3b in DCs did not lead to augmented expression of b-catenin protein, suggesting that GSK-3b exerts its function independent of b-catenin. Supporting this notion, our single cell RNA sequencing (scRNA-seq) analysis revealed that GSK-3b-deficient DCs exhibited distinct gene expression patterns with minimally overlapping differentially expressed genes (DEGs) compared to DCs with activated b-catenin. This suggests that deletion of GSK-3b in DCs is unlikely to lead to upregulation of b-catenin at the transcriptional level. Consistent with enhanced anti-tumor immunity, we also found that CD11c-GSK-3b-/- mice exhibited significantly augmented cross-priming of antigen-specific CD8 T cells following DC-targeted vaccines. We further found that deletion of GSK-3b in DCs completely abrogated memory CD8 T cell responses, suggesting that GSK-3b in DCs also plays a negative role in regulating the differentiation and/or maintenance of memory CD8 T cells. scRNA-seq analysis further revealed that although deletion of GSK-3b in DCs positively regulated transcriptional programs for effector differentiation and function of primed antigen-specific CD8 T cells in CD11c-GSK-3b-/- mice during the priming phase, it resulted in significantly reduced antigen-specific memory CD8 T cells, consistent with diminished memory responses. Taken together, our data demonstrate that GSK-3b in DCs has opposite functions in regulating cross-priming and memory CD8 T cell responses, and GSK-3b exerts its functions independent of its regulation of b-catenin.
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Project description:The two vertebrate Gsk-3 isoforms, Gsk-3a and Gsk-3b, are encoded by distinct genetic loci and exhibit mostly redundant function in murine embryonic stem cells (ESCs). Here we report that deletion of both Gsk-3a and Gsk-3b in mouse ESCs results in misregulated expression of imprinted genes and hypomethylation of corresponding imprinted loci. Treatment of wild-type ESCs with small molecule inhibitors of Gsk-3 phenocopies the DNA hypomethylation of imprinted loci observed in Gsk-3 null ESCs. We provide evidence that DNA hypomethylation in Gsk-3 null ESCs is due to a reduction in the levels of the de novo DNA methyltransferase, Dnmt3a2. Gsk-3 activity serves as a node for several signal transduction pathways, and its regulation of Dnmt3a2 expression raises the possibility that DNA methylation could be transiently affected by different types of environmental stimuli. Our data suggest that modulating Gsk-3 activity could have further reaching effects in the regulation of the epigenome. Keywords: Gene expression array-based The study was designed to examine the changes in gene expression between wild-type and Gsk-3a-/-;Gsk-3b-/- mouse embryonic stem cells.
2010-11-15 | E-GEOD-20015 | biostudies-arrayexpress
Project description:The two vertebrate Gsk-3 isoforms, Gsk-3a and Gsk-3b, are encoded by distinct genetic loci and exhibit mostly redundant function in murine embryonic stem cells (ESCs). Here we report that deletion of both Gsk-3a and Gsk-3b in mouse ESCs results in misregulated expression of imprinted genes and hypomethylation of corresponding imprinted loci. Treatment of wild-type ESCs with small molecule inhibitors of Gsk-3 phenocopies the DNA hypomethylation of imprinted loci observed in Gsk-3 null ESCs. We provide evidence that DNA hypomethylation in Gsk-3 null ESCs is due to a reduction in the levels of the de novo DNA methyltransferase, Dnmt3a2. Gsk-3 activity serves as a node for several signal transduction pathways, and its regulation of Dnmt3a2 expression raises the possibility that DNA methylation could be transiently affected by different types of environmental stimuli. Our data suggest that modulating Gsk-3 activity could have further reaching effects in the regulation of the epigenome. Keywords: Gene expression array-based
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Project description:Gene expression data from AML cell lines, MOLM-14, U937, THP-1 and HL-60, that were infected with a scrambled control hairpin (shControl), two shRNAs directed against GSK-3B (shGSK3B_1 and shGSK3B_2), or two shRNAs directed against GSK-3A (shGSK3A_5 and shGSK3A_6). Acute myeloid leukemia (AML) is the most common form of acute leukemia in adults. Long-term survival of patients with AML has changed little over the past decade, necessitating the identification and validation of new AML targets. Integration of genomic approaches with small-molecule and genetic-based high-throughput screening holds the promise of improved discovery of candidate targets for cancer therapy. Here, we identified a role for glycogen synthase kinase 3A (GSK-3A) in AML by performing two independent small-molecule library screens and an shRNA screen for perturbations that induced a differentiation expression signature in AML cells. GSK-3 is a serine-threonine kinase involved in diverse cellular processes including differentiation, signal transduction, cell cycle regulation, and proliferation. We demonstrated that specific loss of GSK-3A induced differentiation in AML by multiple measurements, including induction of gene expression signatures, morphological changes, and cell surface markers consistent with myeloid maturation. GSK-3AM-bM-^@M-^Sspecific suppression also led to impaired growth and proliferation in vitro, induction of apoptosis, loss of colony formation in methylcellulose, and anti-AML activity in vivo. Although the role of GSK-3B has been well studied in cancer development, these studies support a role for GSK-3A in AML. The AML cell lines, MOLM-14, U937, THP-1 and HL-60, were infected with a scrambled control hairpin (shControl), two shRNAs directed against GSK-3B (shGSK3B_1 and shGSK3B_2), and two shRNAs directed against GSK-3A (shGSK3A_5 and shGSK3A_6).
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