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GSE8498
Mus musculus
6 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Both microRNAs and alternative pre-mRNA splicing have been implicated in the development of the nervous system (NS), but functional interactions between these two pathways are poorly understood. We demonstrate that the neuron-specific microRNA miR-124a directly targets PTBP1/PTB/hnRNPI mRNA, which encodes a global repressor of alternative pre-mRNA splicing in non-neuronal cells. Among the targets of PTBP1 is a critical cassette exon in the pre-mRNA of PTBP2/nPTB/brPTB, an NS-enriched PTBP1 homolog. When this exon is skipped, PTBP2 mRNA is subject to nonsense-mediated decay. During neuronal differentiation, miR-124a reduces PTBP1 levels leading to the accumulation of correctly spliced PTBP2 mRNA and a dramatic increase in PTBP2 protein. These events culminate in the transition from non-NS to NS-specific alternative splicing patterns. We also present evidence that miR-124a plays a key role in the differentiation of progenitor cells to mature neurons. Thus, miR-124a promotes NS development at least in part by regulating an intricate network of NS-specific alternative splicing.
Publication Title
The MicroRNA miR-124 promotes neuronal differentiation by triggering brain-specific alternative pre-mRNA splicing.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 2 Downloadable Samples
Illumina HiSeq 2500
Description
Nervous system (NS) development relies on coherent up-regulation of extensive sets of genes in a precise spatiotemporal manner. How such transcriptome-wide effects are orchestrated at the molecular level remains an open question. Here we show that 3'-untranslated regions (3'UTRs) of multiple neuronal transcripts contain A/U-rich cis-elements (AREs) recognized by tristetraprolin (TTP/Zfp36), an RNA-binding protein previously reported to destabilize mRNAs encoding predominantly cytokines, growth factors and proto-oncogenes. We further demonstrate that the efficiency of ARE-dependent mRNA degradation declines during neural differentiation due to a decrease in the TTP protein expression mediated by the NS-enriched microRNA miR-9. Our experiments with transgenenic cell lines suggest that TTP down-regulation is essential for proper neuronal differentiation. Moreover, inactivation of TTP in neuroblastoma cells or mouse embryonic fibroblasts induces major changes in their transcriptomes accompanied by significantly elevated expression of NS-specific genes. We conclude that the newly identified miR-9/TTP circuitry limits unscheduled accumulation of neuronal mRNAs in non-neuronal cells and ensures coordinated up-regulation of these transcripts in neurons. Overall design: 3''READS of undifferentiated and 3.5-day differentiated P19 cells
Publication Title
A post-transcriptional mechanism pacing expression of neural genes with precursor cell differentiation status.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 20 Downloadable Samples
- NextSeq 500
Description
The generation of induced pluripotent stem cells (iPSCs) and the direct conversion approach provide an invaluable resource of cells for disease modeling, drug screening, and patient-specific cell-based therapy. However, while iPSCs are stable and resemble ESCs in their transcriptome, methylome and function, the vast majority of the directly converted cells represent an incomplete reprogramming state as evident by their aberrant transcriptome and transgene dependency. This raises the question of whether complete and stable nuclear reprogramming can be achieved only in pluripotent cells. Here we demonstrate the generation of stable and fully functional induced trophoblast stem cells (iTSCs) by transient expression of Gata3, Tfap2c and Eomes. Similarly to iPSCs, iTSCs underwent a complete and stable reprogramming process as assessed by transcriptome and methylome analyses and functional assays such as the formation of hemorrhagic lesion and placenta contribution. Careful examination of the conversion process indicated that the cells did not go through a transient pluripotent state. These results suggest that complete nuclear reprograming can be attained in non-pluripotent cells. Overall design: Technical duplicates of 10 samples
Publication Title
Extensive Nuclear Reprogramming Underlies Lineage Conversion into Functional Trophoblast Stem-like Cells.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 3 Downloadable Samples
- Illumina human-6 v2.0 expression beadchip
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Patterns of histone H3 lysine 27 monomethylation and erythroid cell type-specific gene expression.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Homo sapiens
- 3 Downloadable Samples
- Illumina human-6 v2.0 expression beadchip
Description
ERYTHROID CELL-TYPE SPECIFIC GENE EXPRESSION
Publication Title
Patterns of histone H3 lysine 27 monomethylation and erythroid cell type-specific gene expression.
Sample Metadata Fields
Cell line
View Samples- Mus musculus
- 4 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Dendritic cells (DCs) regulate both innate and adaptive immune responses.
Publication Title
Early responding dendritic cells direct the local NK response to control herpes simplex virus 1 infection within the cornea.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 15 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Differentiation of muscle tissue is regulated by a complex network of transcription factors. The MEF2 family of transcription factors are important players in muscle development and differentiation.
Publication Title
MEF2 transcription factors regulate distinct gene programs in mammalian skeletal muscle differentiation.
Sample Metadata Fields
Cell line
View Samples- Homo sapiens
- 3 Downloadable Samples
- Illumina HumanWG-6 v3.0 expression beadchip
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Stability of gene expression and epigenetic profiles highlights the utility of patient-derived paediatric acute lymphoblastic leukaemia xenografts for investigating molecular mechanisms of drug resistance.
Sample Metadata Fields
Sex
View Samples- Homo sapiens
- 3 Downloadable Samples
- Illumina HumanWG-6 v3.0 expression beadchip
Description
Background: Patient-derived tumour xenografts are an attractive model for preclinical testing of anti-cancer drugs. Insights into tumour biology and biomarkers predictive of responses to chemotherapeutic drugs can also be gained from investigating xenograft models. As a first step towards examining the equivalence of epigenetic profiles between xenografts and primary tumours in paediatric leukaemia, we performed genome-scale DNA methylation and gene expression profiling on a panel of 10 paediatric B-cell precursor acute lymphoblastic leukaemia (BCP-ALL) tumours that were stratified by prednisolone response. Results: We found high correlations in DNA methylation and gene expression profiles between matching primary and xenograft tumour samples with Pearsons correlation coefficients ranging between 0.85 and 0.98. In order to demonstrate the potential utility of epigenetic analyses in BCPALL xenografts, we identified DNA methylation biomarkers that correlated with prednisolone responsiveness of the original tumour samples. Differential methylation of CAPS2, ARHGAP21, ARX and HOXB6 were confirmed by locus specific analysis. We identified 20 genes showing an inverse relationship between DNA methylation and gene expression in association with prednisolone response. Pathway analysis of these genes implicated apoptosis, cell signalling and cell structure networks in prednisolone responsiveness. Conclusions: The findings of this study confirm the stability of epigenetic and gene expression profiles of paediatric BCP-ALL propagated in mouse xenograft models. Further, our preliminary investigation of prednisolone sensitivity highlights the utility of mouse xenograft models for preclinical development of novel drug regimens with parallel investigation of underlying gene expression and epigenetic responses associated with novel drug responses.
Publication Title
Stability of gene expression and epigenetic profiles highlights the utility of patient-derived paediatric acute lymphoblastic leukaemia xenografts for investigating molecular mechanisms of drug resistance.
Sample Metadata Fields
Sex
View Samples- Mus musculus
- 3 Downloadable Samples
- Illumina HiSeq 2000
Description
HM1, HP1a-/-, and HP1b-/- ESC transcriptomes were generated to determine whether depletion of these HP1 proteins influences gene and/or retroelement expression Overall design: mRNA profiles of HP1a and HP1b Knockouts and its corresponding wildtype
Publication Title
Distinct roles of KAP1, HP1 and G9a/GLP in silencing of the two-cell-specific retrotransposon MERVL in mouse ES cells.
Sample Metadata Fields
Specimen part, Subject
View Samples