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GSE77080
Homo sapiens
36 Downloadable Samples
Illumina HumanHT-12 V4.0 expression beadchip
Description
The number of long-term survivors of high-risk neuroblastoma remains discouraging, with 10-year survival as low as 20%, despite decades of considerable international efforts to improve outcome. Major obstacles remain and include managing resistance to induction therapy, which causes tumor progression and early death in high-risk patients, and managing chemotherapy-resistant relapses, which can occur years after the initial diagnosis. Identifying and validating novel therapeutic targets is essential to improve treatment. Delineating and deciphering specific functions of single histone deacetylases in neuroblastoma may support development of targeted acetylome-modifying therapeutics for patients with molecularly defined high-risk neuroblastoma profiles. We show here that HDAC11 depletion in MYCN-driven neuroblastoma cell lines strongly induces cell death, mostly mediated by apoptotic programs. Genes necessary for mitotic cell cycle progression and cell division were most prominently enriched in at least two of three time points in whole-genome expression data combined from two cell systems, and all nine genes in these functional categories were strongly repressed, including CENPA, KIF14, KIF23 and RACGAP1. Enforced expression of one selected candidate, RACGAP1, partially rescued the induction of apoptosis caused by HDAC11 depletion. High-level expression of all nine genes in primary neuroblastomas signicantly correlated with unfavorable overall and event-free survival in patients, suggesting a role in mediating the more aggressive biological and clinical phenotype of these tumors. Our study identied a group of cell cycle-promoting genes regulated by HDAC11, being both predictors of unfavorable patient outcome and essential for tumor cell viability. The data indicates a signicant role of HDAC11 for mitotic cell cycle progression and survival of MYCN-amplified neuroblastoma cells, and suggests that HDAC11 could be a valuable drug target.
Publication Title
Neuroblastoma cells depend on HDAC11 for mitotic cell cycle progression and survival.
Sample Metadata Fields
Cell line, Time
View Samples- Mus musculus
- 4 Downloadable Samples
- Affymetrix Mouse Gene 2.0 ST Array (mogene20st)
Description
Erythropoiesis is essential to mammals and is regulated at multiple steps by both extracellular and intracellular factors. Many transcriptional regulatory networks in erythroid differentiation have been well characterized. However, our understanding of post-transcriptional regulatory circuitries in this developmental process is still limited. Using genomic approaches, we identified a sequence-specific RNA-binding protein, Cpeb4, which is dramatically induced in terminal erythroid differentiation (TED) by two erythroid important transcription factors, Gata1/Tal1. Cpeb4 belongs to the cytoplasmic polyadenylation element binding (CPEB) protein family that regulates translation of target mRNAs in early embryonic development, neuronal synapse, and cancer. Using primary mouse fetal liver erythroblasts, we found that Cpeb4 is required for terminal erythropoiesis by repressing the translation of a set of mRNAs highly expressed in progenitor cells. This translational repression occurs by the interaction with a general translational initiation factor, eIF3. Interestingly, Cpeb4 also binds its own mRNA and represses its translation, thus forming a negative regulatory circuitry to limit Cpeb4 protein level. This mechanism ensures that the translation repressor, Cpeb4, does not interfere with the translation of other mRNAs in differentiating erythroblasts. Our study characterized a translational regulatorycircuitry that controls TED and revealed that Cpeb4 is required for somatic cell differentiation.
Publication Title
Cpeb4-mediated translational regulatory circuitry controls terminal erythroid differentiation.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 11 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Primary murine fetal liver cells were freshly isolated from day e14.5 livers and then sorted for successive differentiation stages by Ter119 and CD71 surface expression (ranging from double-negative CFU-Es to Ter-119 positive enucleated erythrocytes) [Zhang, et al. Blood. 2003 Dec 1; 102(12):3938-46]. RNA isolated from each freshly isolated, stage-sorted population was reverse-transcribed, labelled, and then hybridized onto 3' oligo Affymetrix arrays. Important erythroid specific genes as well as the proteins that regulate them were elucidated through this profiling based on coexpression and differential expression patterns as well as by extracting specific GO categories of genes (such as DNA-binding proteins).
Publication Title
Homeodomain-interacting protein kinase 2 plays an important role in normal terminal erythroid differentiation.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 35 Downloadable Samples
- Affymetrix Human Exon 1.0 ST Array [transcript (gene) version (huex10st)
Description
In this study, mRNA expression profiles of 113 primary untreated human neuroblastoma samples were compared with the aim to identify prognostic exon and gene sets as well as parameters associated with alternative exon use. The primary neuroblastoma specimens were from tumor banks in Cologne or Essen, Germany, Ghent, Belgium and Valencia, Spain. All patients were diagnosed between 1998 and 2007 and treated according to the German Neuroblastoma trials NB97, NB 2004 or the SIOPEN protocol.
Publication Title
Smac mimetic LBW242 sensitizes XIAP-overexpressing neuroblastoma cells for TNF-α-independent apoptosis.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Mus musculus
- 32 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Infection of RAW264.7 cells for 24 hours with 32 Toxoplasma Progeny from a Type II x Type III cross
Publication Title
GRA25 is a novel virulence factor of Toxoplasma gondii and influences the host immune response.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Objective : To study molecular changes in the articular cartilage and subchondral bone of the tibial plateau from mice deficient in frizzled related protein (Frzb) compared to wild-type mice by transcriptome analysis.
Publication Title
Tight regulation of wingless-type signaling in the articular cartilage - subchondral bone biomechanical unit: transcriptomics in Frzb-knockout mice.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Homo sapiens
- 4 Downloadable Samples
Illumina Genome Analyzer
Description
To better understand the mechanisms of blockage of myeloid differentiation and apoptosis and induction of proliferation by miR-125b, we proceeded to identify miR-125b target genes involved in these pathways. We analyzed the total cellular gene expression pattern by RNA-sequencing of the parental NB4 myeloid cell line and that transiently transfected with miR-125b. We generated four cDNA libraries corresponding to duplicates of miR-125b and control cells. Overall design: Compare the gene expression levels in miR control transfected cells with that in miR-125b transfected NB4 cells.Â
Publication Title
MicroRNA-125b transforms myeloid cell lines by repressing multiple mRNA.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Mus musculus
- 4 Downloadable Samples
- Illumina Genome Analyzer
Description
To better understand the mechanisms of blockage of myeloid differentiation and apoptosis and induction of proliferation by miR-125b, we preceded to identify miR-125b target genes involved in these pathways. We analyzed the total cellular gene expression pattern by RNA-sequencing of the parental 32Dclone3 myeloid cell line and that ectopically expressing miR-125b. We generated four cDNA libraries corresponding to duplicates of miR-125b and control cells. Overall design: Compare the gene expression level in vector transduced 32Dclone3 cells with that in miR-125b transduced 32Dclone3 cells.Â
Publication Title
MicroRNA-125b transforms myeloid cell lines by repressing multiple mRNA.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Mus musculus
- 2 Downloadable Samples
- Illumina Genome Analyzer II
Description
Using RNA-seq technology, we quantitatively determined the expression profile of microRNAs during mouse terminal erythroid differentiation. CFU-E erythroid progenitors were isolated from E14.5 fetal liver as the Ter119, B220, Mac-1, CD3 and Gr-1 negative, C-Kit positive and 20% high CD71 population. Mature Ter119+ erythroblasts were isolated from E14.5 fetal liver as C-Kit negative and Ter119 positive population. Consistent with nuclear condensation and global gene expression shut down during terminal erythroid differentiation, we found that the majority of microRNAs are downregulated in more mature Ter119+ erythroblasts compared with CFU-E erythroid progenitors. Overall design: Examination of microRNA expression profiles in 2 cell types
Publication Title
miR-191 regulates mouse erythroblast enucleation by down-regulating Riok3 and Mxi1.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 24 Downloadable Samples
- Affymetrix Mouse Expression 430A Array (moe430a)
Description
Inherited genetic risk factors play an important role in cancer. However, other than cancer susceptibility genes found in familial cancer syndromes and inherited in a Mendelian fashion, little is known about modifier genes (germline variants that interact with each other and with environmental factors) that contribute to individual susceptibility. Here we develop a strategy parental strain expression mapping (PSEM), which utilizes the homogeneity of inbred mice and genome-wide mRNA expression analyses, to directly identify candidate germline modifier genes and pathways underlying phenotypic differences among murine strains exposed to transgenic activation of AKT1. We identified multiple candidate modifier pathways and specifically, the glycolysis pathway as a candidate negative modulator of AKT1-induced proliferation. In keeping with findings in murine models, the expression of the glycolysis pathway was strongly enriched in the non-cancer prostate tissue from patients with prostate cancer who did not recur after surgical resection. Together these data suggest that PSEM can directly identify germline modifier pathways of relevance to human disease.
Publication Title
Identification of prostate cancer modifier pathways using parental strain expression mapping.
Sample Metadata Fields
Age
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