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GSE27174
Mus musculus
8 Downloadable Samples
Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Lineage-specific transcription factors, which drive cellular identity during embryogenesis, have been shown to convert cell fate when express ectopically in heterologous cells. Herein, we screened the key molecular factors governing the dopaminergic neuronal specification during brain development for their ability to generate similar neurons directly from mouse and human fibroblasts. Remarkably, we found a minimal set of three factors Mash1, Nurr1 and Lmx1a/b able to elicit such cellular reprogramming. Molecular and transcriptome studies showed reprogrammed DA neurons to faithfully recapitulate gene expression of their brain homolog cells while lacking expression of other catecholaminergic neuronal types. Induced neurons showed spontaneous electrical activity organized in regular spikes consistent with the pacemaker activity featured by brain DA neurons. The three factors were able to elicit DA neuronal conversion in human fibroblasts from prenatal or adult fibroblasts of healthy donors and a Parkinsons disease patient. Generation of DA induced neurons from somatic cells might have significant implications in studies of neural development, disease in vitro modeling and cell replacement therapies.
Publication Title
Direct generation of functional dopaminergic neurons from mouse and human fibroblasts.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 6 Downloadable Samples
IlluminaHiSeq1000
Description
Human SH-SY5Y neuroblastoma cells are widely utilized in in vitro studies to dissect out pathogenetic mechanisms of neurodegenerative disorders. These cells are considered as neuronal precursors and differentiate into more mature neuronal phenotypes under selected growth conditions. In this study, we performed systematic transcriptomic (RNA-seq) and bioinformatic analysis to pinpoint pathways and cellular processes underlying neuronal differentiation of SH-SY5Y cells according to a two-step paradigm: retinoic acid treatment followed by enriched neurobasal medium. Categorization of 1989 differentially expressed genes (DEGs) identified in differentiated cells outlined meaningful biological functions associated with changes in cell morphology including remodelling of plasma membrane and cytoskeleton, neuritogenesis. Seventy-three DEGs were assigned to Axonal Guidance Signalling pathway, and the expression of selected gene products such as neurotrophin receptors, the functionally related SLITRK6, and semaphorins, was validated by immunoblotting. Along with these findings, the differentiated cells exhibited the ability to elongate longer axonal process as assessed by the morphometric evaluation. Recognition of molecular events occurring in differentiated SH-SY5Y cells is necessary to accurately interpret the cellular responses to specific stimuli in studies on disease pathogenesis. Overall design: Comparison of cell line SH-SY5Y differentiated and undifferentiated.
Publication Title
Transcriptomic Profiling Discloses Molecular and Cellular Events Related to Neuronal Differentiation in SH-SY5Y Neuroblastoma Cells.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 139 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Gene expression analysis identified a MLL translocation-specific signature of differentially expressed genes discriminating ALL and AML with and without MLL rearrangements.
Publication Title
MLL rearrangements in pediatric acute lymphoblastic and myeloblastic leukemias: MLL specific and lineage specific signatures.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 18 Downloadable Samples
- Illumina HiSeq 2500
Description
Transplantation of GABAergic interneurons (INs) can sustain long-standing benefits in animal models of epilepsy and other neurological disorders. In a therapeutic perspective, a renewable source of functional GABAergic INs is needed. Here, we identified five factors (Foxg1, Sox2, Ascl1, Dlx5 and Lhx6) able to convert fibroblasts directly into induced GABAergic INs (iGABA-INs), displaying the molecular signature of telencephalic INs. The selected factors recapitulate in fibroblasts the activation of transcriptional networks required for the specification of GABAergic fate during telencephalon development. iGABA-INs exhibited progressively maturing firing patterns comparable to those of cortical INs, had synaptic currents and released GABA. Importantly, upon grafting in the hippocampus, iGABA-INs survived, matured and their optogenetic stimulation triggered GABAergic transmission and inhibited the activity of connected granule cells. The five factors also converted human cells into functional GABAergic neurons. These properties define iGABA-INs as a promising tool for disease modeling and cell-based therapeutic approaches. Overall design: Comparison of iGABA-INs transcriptional profile with those of starting fibroblasts and GAD67-GFP+ cortical interneurons.
Publication Title
Rapid Conversion of Fibroblasts into Functional Forebrain GABAergic Interneurons by Direct Genetic Reprogramming.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Homo sapiens
- 96 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Microarray gene expression (MAGE) signatures allow insights into the transcriptional processes of leukemias and may evolve as a molecular diagnostic test. Introduction of MAGE into clinical practice of leukemia diagnosis will require comprehensive assessment of variation due to the methodologies.
Publication Title
New data on robustness of gene expression signatures in leukemia: comparison of three distinct total RNA preparation procedures.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 4 Downloadable Samples
- Illumina HiSeq 2500
Description
We created two cell lines derived from Ovcar8 by stably transfecting with an eGFP-firefly luciferase fusion protein and either an additional copy of the gene TWIST1 or an shRNA against TWIST1, under the control of the CMV promoter. RNA sequencing was used to look for differential expression of genes that may impact cisplatin resistance in epithelial ovarian cancer. Overall design: RNA-seq for differential expression between two cell lines differing in expression of gene of interest. Run as biological replicates and technical triplicates.
Publication Title
TWIST1 drives cisplatin resistance and cell survival in an ovarian cancer model, via upregulation of GAS6, L1CAM, and Akt signalling.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Homo sapiens
- 97 Downloadable Samples
- Illumina HumanHT-12 V3.0 expression beadchip
Description
Genomic and expression profiling using 38K BAC array-CGH and Illumina HT-12 beadchips were performed on 97 diploid invasive breast tumors to assess the impact of gene dosage on gene expression patterns and the effect of other mechanisms on transcriptional levels. Patient stratification was performed according to axillary lymph node status (node-negative, pN0; node-positive, pN1) and overall survival (>8-year survivors; breast cancer-specific mortality within 8 years of diagnosis). Array-CGH results was validated by FISH using tumors showing HER2/neu gene amplification and expression profiling was confirmed using qPCR for 16 transcripts.
Publication Title
Clinical implications of gene dosage and gene expression patterns in diploid breast carcinoma.
Sample Metadata Fields
Disease, Disease stage
View Samples- Homo sapiens
- 97 Downloadable Samples
- Illumina HumanHT-12 V3.0 expression beadchip
Description
Genomic and expression profiling using 38K BAC array-CGH and Illumina HT-12 beadchips were performed on 97 diploid invasive breast tumors to assess the impact of gene dosage on gene expression patterns and the effect of other mechanisms on transcriptional levels. Patient stratification was performed according to axillary lymph node status (node-negative, pN0; node-positive, pN1) and overall survival (>8-year survivors; breast cancer-specific mortality within 8 years of diagnosis). Array-CGH results was validated by FISH using tumors showing HER2/neu gene amplification and expression profiling was confirmed using qPCR for 16 transcripts.
Publication Title
Clinical implications of gene dosage and gene expression patterns in diploid breast carcinoma.
Sample Metadata Fields
Disease, Disease stage
View Samples- Homo sapiens
- 53 Downloadable Samples
- Illumina HumanHT-12 V3.0 expression beadchip
Description
Transcriptomic profiling of human breast tumors.
Publication Title
Clinical implications of gene dosage and gene expression patterns in diploid breast carcinoma.
Sample Metadata Fields
Age, Specimen part
View Samples- Mus musculus
- 4 Downloadable Samples
- Illumina HiSeq 2000
Description
Purpose: Analyze the function of the transcription factors Hand2 and Gata3 in adult sympathetic neurons by induced knockout and RNAseq analysis Overall design: Method and Result: Hand2flx/del::DbhCreERT2 (referred to as mutant) and Hand2flx/+::DbhCreERT2 (referred to a control) were injected for 10 days with tamoxifen to activate Cre. Animals were killed, sympathetic ganglia (SCG+Stellate) collected and processed for RNA isolation and RNAseq (Stanzel et al., 2016). Gata3flx/flx::DbhCerERT2 (mutant) and Gata3flx/+::DbhCreERT2 (controls) were treated as Hand2 animals. 16 ganglia from 4 mice were pooled for Hand2 mutant and controls and Gata3 controls. As only rudimentary ganglia were present in Gata3 mutant mice (Tsarovina et al., 2010) ganglia from 8 mice were pooled. The specific effects of the Hand2 knockout are decribed in Stanzel et al., 2016. The analysis of ganglion rudiments in the Gata3 knockout revealed that Gata3 was not reduced, indicating that the remaining cells had escaped the knockout.
Publication Title
Distinct roles of hand2 in developing and adult autonomic neurons.
Sample Metadata Fields
Specimen part, Subject
View Samples