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GSE50933
Mus musculus
10 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Thymic iNKT cell development is divided into four stages (stage 0-3) that are characterised, in C57BL/6 mouse strain, by the differential expression of surface markers, such as CD24, CD44 and NK1.1. During transition from immature to mature iNKT cell subsets, gene expression is tightly regulated. Here, we used microarray analysis to detail the influence of the transcriptional regulator ID3 during iNKT cell maturation in the thymus.
Publication Title
Essential functions for ID proteins at multiple checkpoints in invariant NKT cell development.
Sample Metadata Fields
Age, Specimen part
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Transcription factor ID2 prevents E proteins from enforcing a naïve T lymphocyte gene program during NK cell development.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 16 Downloadable Samples
Illumina HiSeq 2500
Description
We identified the ubiquitin ligase Huwe1 as a crucial regulator of hematopoietic stem cell (HSC) functions. We generated Huwe1 conditional knock-out mice and discovered that the loss of this ligase causes an increased proliferation and stem cell exhaustion, together with a decreased lymphoid specification in vivo. We observed that the ubiquitin ligase Huwe1 is controlling the expression of N-myc at the level of the most immature stem and progenitor hematopoietic populations, mediating the described effects. Overall design: High-troughput RNA-sequencing of sorted HSC (Lin-Sca+Kit+CD48-CD150+) from wild type or Huwe1 conditional knockout mice (constitutively deleted with Vav-Cre recombinase or inducibly deleted with Mx1-Cre)
Publication Title
The ubiquitin ligase Huwe1 regulates the maintenance and lymphoid commitment of hematopoietic stem cells.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 10 Downloadable Samples
- Affymetrix Human Genome U133B Array (hgu133b), Affymetrix Human Genome U133A Array (hgu133a)
Description
E47 is a basic Helix Loop Helix (bHLH) transcription factor that has important roles in cell fate determination and differentiation of many cell types. In the nervous system E47 heterodimerizes with tissue-specific, pro-neural bHLH transcription factors and activates downstream target genes. To identify the relevant target genes of bHLH transcription factors in neural cells, we performed gene expression profiling of the human neuroblastoma cell line SK-N-SH engineered to acutely express ectopic E47 by an adenoviral vector. The experiments were done at two time points following adenoviral infection, 8 hours and 20 hours. Genes induced by E47 after 8 hours are likely to be direct targets of this transcription factor.
Publication Title
Degradation of Id2 by the anaphase-promoting complex couples cell cycle exit and axonal growth.
Sample Metadata Fields
Specimen part, Cell line, Time
View Samples- Mus musculus
- 8 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Differentiation of naive CD4+ T cells into T-helper (Th) effector subsets is critical for protection against pathogens. Together, E-protein transcription factors and the inhibitor-of-DNA binding (Id) proteins are important arbiters of T cell development, but their role in the differentiation of Th1 and Tfh cells is not well understood. Th1 cells show robust Id2 expression compared to Tfh cells, and RNAi depletion of Id2 increased Tfh cell frequencies and germinal center responses, while impairing Th1 cell accumulation during viral infection. Further, Th1 cell differentiation was blocked by genetic ablation of Id2, leading to E-protein dependent accumulation of effector cells with 78% of Th1-associated genes showing diminished expression and a concurrent enrichment of the Tfh gene-expression program. The Tfh-defining transcriptional repressor Bcl6 bound to the Id2 locus inhibiting expression, providing a mechanism by which bimodal expression of Id2 in Tfh and Th1 cells can be established. Thus, Id2 is critical in enforcing the reciprocal development of Th1 and Tfh cell fates.
Publication Title
Id2 reinforces TH1 differentiation and inhibits E2A to repress TFH differentiation.
Sample Metadata Fields
Age, Specimen part
View Samples- Mus musculus, Homo sapiens
- 2 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
ETO family protein Mtg16 regulates the balance of dendritic cell subsets by repressing Id2.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Mus musculus
- 4 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
We identified the ubiquitin ligase Huwe1 as a crucial regulator of hematopoietic stem cell (HSC) functions. We generated Huwe1 conditional knock-out mice and discovered that the loss of this ligase causes an increased proliferation and stem cell exhaustion, together with a decreased lymphoid specification in vivo. We observed that the ubiquitin ligase Huwe1 is controlling the expression of N-myc at the level of the most immature stem and progenitor hematopoietic populations, mediating the described effects.
Publication Title
The ubiquitin ligase Huwe1 regulates the maintenance and lymphoid commitment of hematopoietic stem cells.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 2 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
E protein transcription factors specify major immune cell lineages including lymphocytes and interferon-producing plasmacytoid dendritic cells (pDCs). Corepressors of the ETO family can bind to and block transactivation by E proteins, but the physiological role of these interactions remained unclear. We report that ETO protein Mtg16 binds chromatin primarily through the pDC-specific E protein E2-2 in human pDCs. Mtg16-deficient mice showed impaired pDC development and functionality, whereas the specification of the classical dendritic cells (cDCs) was enhanced. The deletion of Mtg16 caused aberrant expression of E protein antagonist Id2 in pDCs. Thus, Mtg16 acts as a cofactor of E2-2 to promote pDC differentiation and restrict cDC development, revealing an unexpected positive role of ETO proteins in E protein activity.
Publication Title
ETO family protein Mtg16 regulates the balance of dendritic cell subsets by repressing Id2.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus, Homo sapiens
- 108 Downloadable Samples
Illumina MouseWG-6 v2.0 expression beadchip
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
The transcriptional network for mesenchymal transformation of brain tumours.
Sample Metadata Fields
Time
View Samples- Homo sapiens
- 74 Downloadable Samples
- Illumina MouseWG-6 v2.0 expression beadchip
Description
Using a novel combination of cellular-network reverse-engineering algorithms and experimental validation assays, we identified a transcriptional module, including six transcription factors that synergistically regulates the mesenchymal signature of malignant glioma. This is a poorly understood molecular phenotype, never observed in normal neural tissue. It represents the hallmark of tumor aggressiveness in high-grade glioma, and its upstream regulation is so far unknown. Overall, the newly discovered transcriptional module regulates >74% of the signature genes, while two of its transcription factors (C/EBP and Stat3) display features of initiators and master regulators of mesenchymal transformation. Ectopic co-expression of C/EBP and Stat3 is sufficient to reprogram neural stem cells along the aberrant mesenchymal lineage, while simultaneously suppressing differentiation along the default neural lineages (neuronal and glial). Conversely, silencing the two transcription factors in human glioma cell lines and glioblastoma-derived tumor initiating cells leads to collapse of the mesenchymal signature with corresponding loss of tumor aggressiveness in vitro and in immunodeficient mice after intracranial injection. In human tumor samples, combined expression of C/EBP and Stat3 correlates with mesenchymal differentiation of primary glioma and is a predictor of poor clinical outcome. Taken together, these results reveal that activation of a small regulatory module inferred from the accurate reconstruction of transcriptional networks is necessary and sufficient to initiate and maintain an aberrant phenotypic state in eukaryotic cells.
Publication Title
The transcriptional network for mesenchymal transformation of brain tumours.
Sample Metadata Fields
Time
View Samples