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GSE48557
Homo sapiens
4 Downloadable Samples
Affymetrix Human Genome U133A Array (hgu133a)
Description
SCL/TAL1, a tissue-specific transcription factor of the basic helix-loop-helix (bHLH) family, and c-Kit, a tyrosine kinase receptor, control hematopoietic stem cell survival and quiescence. Here we report that SCL and c-Kit signaling control a common gene expression signature, of which 19 genes are associated with apoptosis. In vivo, SCL levels are limiting for the clonal expansion of Kit+ multipotent and erythroid progenitors. In addition, increased SCL expression specifically enhances the sensitivity of multipotent and megakaryocyte/erythroid progenitors to Steel factor (KIT ligand), whilst a DNA binding mutant antagonizes KIT function and induces apoptosis in progenitors. We conclude that Scl operates downstream of Kit to support the survival of megakaryocyte/erythroid progenitors. Finally, higher SCL expression upregulates Kit in normal bone marrow cells and increases chimerism after bone marrow transplantation, indicating that Scl is also upstream of Kit. We conclude that Scl and Kit establish a positive feedback loop in multipotent and megakaryocyte/erythroid progenitors.
Publication Title
Genetic interaction between Kit and Scl.
Sample Metadata Fields
Cell line, Treatment
View Samples- Mus musculus
- 24 Downloadable Samples
Illumina HiSeq 2500
Description
Purpose: Conducted expression profiling by RNA-seq as unbiased screen to identify genes that are altered in motor neurons of PbxMN? mice at e12.5 at brachial and thoracic levels of the spinal cord. Because loss of Pbx genes affects MN organization at all rostrocaudal levels, we focused on genes whose profiles were altered at both brachial and thoracic levels. Methods: We compared gene expression profiles in MNs isolated from control Hb9::GFP and PbxMN?; Hb9::GFP embryos at e12.5. MNs were purified by FACS, and RNA was extracted from 9 PbxMN?; Hb9::GFP and 9 control Hb9::GFP embryos at brachial and thoracic levels using the Arcturus Picopure RNA isolation kit. 10ng of RNA was pooled from 3 RNA samples of each genotype, and used to amplify 100ng of cDNA using Nugene''s Ovation RNA-Seq System V2 kit, 100ng of cDNA for each sample was used as in input to prepare 12 bar coded libraries using the Ovation Ultralow Library system. We then performed expression profiling by RNA-seq. The samples were mixed into two pools and run on two 50-nucleotide paired end read rapid run flow cell lanes with the Illumina HiSeq 2500 sequencer. Generating on average 74 and 101 million reads passing filter for brachial and thoracic samples respectively. Results: This analysis yielded 64 brachial and 124 thoracic genes that were differentially expressed with a stringent cutoff of padj.<0.05. Of these genes, we found 31 genes in common between the two, brachial and thoracic, levels of the spinal cord that may play a role in motor neuron columnar organization. Furthermore our expression profiling of control brachial and control thoracic MNs identified 61 genes with (padj.<0.05), that represent distinct molecular profiles of MNs generated at brachial and thoracic levels which may be used to further characterize MNs involved in forelimb and thoracic innervation. Conclusions: Our study represents a detailed transcriptional analysis of embryonic spinal motor neurons and revealed a number of novel motor neuron-specific genes that are under transcriptional regulation of Pbx genes. Overall design: Examination of embryonic spinal MN expression profiles at 2 different spinal cord levels, brachial and thoracic. From RNA collected from 9 pooled Control and 9 PbxMN? e12.5 Hb9::GFP FACS MNs.
Publication Title
Parallel Pbx-Dependent Pathways Govern the Coalescence and Fate of Motor Columns.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Arabidopsis thaliana
- 63 Downloadable Samples
- Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)
Description
Living organisms have to cope with multiple and combined fluctuations in their environment. According to their sessile mode of life, plants are even more subjected to such fluctuations impacting their physiology and development. In particular, nutrient availability is known to tune plant development through modulating hormonal signaling, and conversely, hormonal signals are key to control nutrient related signaling pathways (Krouk et al., 2011a). However, very few is known about molecular mechanisms leading to plant adaptation to such combined signals. Here we deployed an unprecedented combinatorial treatment matrix to reveal plant adaptation in response to nitrate (NO3-), ammonium (NH4+), auxin (IAA), cytokinins (CK) and abscisic acid (ABA) and their exhaustive binary combinations.
Publication Title
Combinatorial interaction network of transcriptomic and phenotypic responses to nitrogen and hormones in the Arabidopsis thaliana root.
Sample Metadata Fields
Specimen part, Time
View Samples- Homo sapiens
- 8 Downloadable Samples
- IlluminaHiSeq2000
Description
Renin, a key component in the regulation of blood pressure in mammals, is produced by the rare and highly specialized juxtaglomerular (JG) cells of the kidney. Although these cells line the media of the glomerular afferent arterioles and share some characteristics with contractile cells, they are filled with lysosome-like organelles where renin is activated and stored for regulated secretion in response to physiological and pathophysiological stimuli. Chronic stimulation of renin release results in a recruitment of new JG cells by the seeming conversion of adjacent smooth muscle cells along the afferent arterioles. Because JG cells rapidly de-differentiate when removed from the kidney, their developmental origin and the mechanism that explains their phenotypic plasticity remain largely unclear. In an effort to overcome this limitation, we have performed RNA expression analysis on four human renin-producing tumors. The most highly expressed genes that were common between the reninomas were subsequently used for in situ hybridization in mouse kidney. Our results add 40 new genes to the list that characterize renin-producing cells and reveal a significant variation in the expression patterns of developing, mature and recruited JG cells. Overall design: RNA-Seq was performed with a HiSeq 2000 on three biopsies of a first reninoma from Paris (Par1B1-B3), one biopsy from a reninoma from Montreal (Mon), two biopsies from a reninoma from Rotterdam (RotB1, B2), and a second reninoma from Paris (Par2) along with a biopsy from adjacent supposedly normal tissue from the same patient (Par2N).
Publication Title
Transcriptome Analysis of Human Reninomas as an Approach to Understanding Juxtaglomerular Cell Biology.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 8 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Targeted resequencing identifies PTCH1 as a major contributor to ocular developmental anomalies and extends the SOX2 regulatory network.
Sample Metadata Fields
Specimen part, Time
View Samples- Mus musculus
- 8 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
SOX2 is the main gene involved in anophthalmia. In order to identify genes regulated by SOX2 transcription factors (genes that could be good candidates to also be involved in ocular development), we studied transcriptomic profiles of murine genetically modified stem cells overexpressing the RAX gene (CCE-Rx cells) after transfection by a siRNA against SOX2 or a scramble siRNA.
Publication Title
Targeted resequencing identifies PTCH1 as a major contributor to ocular developmental anomalies and extends the SOX2 regulatory network.
Sample Metadata Fields
Specimen part, Time
View Samples- Homo sapiens
- 26 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
CD34 positive cells of bone marrow samples from normal and MDS samples were cultured ex vivo into erythroid conditions.
Publication Title
Defective nuclear localization of Hsp70 is associated with dyserythropoiesis and GATA-1 cleavage in myelodysplastic syndromes.
Sample Metadata Fields
Specimen part
View Samples- Gallus gallus
- 12 Downloadable Samples
- Affymetrix Chicken Genome Array (chicken)
Description
The proneural NEUROG2 is essential for neuronal commitment, cell cycle exit and neuronal differentiation. Characterizing genes networks regulated downstream of NEUROG2 is therefore of prime importance. To identify NEUROG2 early response genes, we combined gain of function in the neural tube with a global detection of modified transcripts using microarrays. We included in our study a mutant form of NEUROG2 (NEUROG2AQ) that cannot bind DNA and cannot trigger neurogenesis. Using this approach, we identified 942 genes modified at the onset of NEUROG2 activation. The global analysis of functions regulated by NEUROG2 allowed unmasking its rapid impact on cell cycle control. We found that NEUROG2 specifically represses a subset of cyclins acting at the G1 and S phases of the cell cycle, thereby impeding S phase re-entry. This repression occurs before modification of p27kip1, indicating that the decision to leave the cell cycle precedes the activation of this Cyclin-dependant Kinase Inhibitor. Moreover, NEUROG2 down-regulates only one of the D-type cyclins, cyclinD1, and maintaining cyclinD1 blocks the ability of the proneural to trigger cell cycle exit, without altering its capacity to trigger neuronal differentiation. The fact that NEUROG2 represses a subset but not all cell cycle regulators indicates that cell cycle exit is not an indirect consequence of neuronal differentiation but is precisely controlled by NEUROG2. Altogether our findings indicate that NEUROG2, by specifically repressing G1 and S cyclins, allows committed neuronal precursors to perform their last mitosis but blocks their re-entry in the cell cycle, thus favouring cell cycle exit.
Publication Title
NEUROG2 drives cell cycle exit of neuronal precursors by specifically repressing a subset of cyclins acting at the G1 and S phases of the cell cycle.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Mus musculus
- 8 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Following the identification of a critical time window of Blood Brain Barrier formation in the mouse embryo, we aimed to identify genes important for barriergenesis. To this end, we isolated cortical and lung E13.5 endothelial cells and compared expression between the two populations.
Publication Title
Mfsd2a is critical for the formation and function of the blood-brain barrier.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 8 Downloadable Samples
- Affymetrix Human Exon 1.0 ST Array [transcript (gene) version (huex10st)
Description
Background: The vast majority of human genes (.70%) are alternatively spliced. Although alternative pre-mRNA processing is modified in multiple tumors, alternative hyper-splicing signatures specific to particular tumor types are still lacking. Here, we report the use of Affymetrix Human Exon Arrays to spot hyper-splicing events characteristic of myasthenia gravis (MG)-thymoma, thymic tumors which develop in patients with MG and discriminate them from colon cancer changes. Methodology/Principal Findings: We combined GO term to parent threshold-based and threshold-independent ad-hoc functional statistics with in-depth analysis of key modified transcripts to highlight various exon-specific changes. These denote alternative splicing in MG-thymoma tumors compared to healthy human thymus and to in-house and Affymetrix datasets from colon cancer and healthy tissues. By using both global and specific, term-to-parent Gene Ontology (GO) statistical comparisons, our functional integrative ad-hoc method allowed the detection of disease-relevant splicing events. Conclusions/Significance: Hyper-spliced transcripts spanned several categories, including the tumorogenic ERBB4 tyrosine kinase receptor and the connective tissue growth factor CTGF, as well as the immune function-related histocompatability gene HLA-DRB1 and interleukin (IL)19, two muscle-specific collagens and one myosin heavy chain gene; intriguingly, a putative new exon was discovered in the MG-involved acetylcholinesterase ACHE gene. Corresponding changes in spliceosome composition were indicated by co-decreases in the splicing factors ASF/SF2 and SC35. Parallel tumor-associated changes occurred in colon cancer as well, but the majority of the apparent hyper-splicing events were particular to MGthymoma and could be validated by Fluorescent In-Situ Hybridization (FISH), Reverse TranscriptionPolymerase Chain Reaction (RT-PCR) and mass spectrometry (MS) followed by peptide sequencing. Our findings demonstrate a particular alternative hyper-splicing signature for transcripts over-expressed in MG-thymoma, supporting the hypothesis that alternative hyper-splicing contributes to shaping the biological functions of these and other specialized tumors and opening new venues for the development of diagnosis and treatment approaches
Publication Title
Identifying alternative hyper-splicing signatures in MG-thymoma by exon arrays.
Sample Metadata Fields
Sex
View Samples