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Homo sapiens
406 Downloadable Samples
IlluminaHiSeq2000
Description
We apply the cellular reprogramming experimental paradigm to two disorders caused by symmetrical copy number variations (CNV) of 7q11.23 and displaying a striking combination of shared as well as symmetrically opposite phenotypes: Williams Beuren syndrome (WBS) and 7q microduplication syndrome (7dupASD). Through a uniquely large and informative cohort of transgene-free patient-derived induced pluripotent stem cells (iPSC), along with their differentiated derivatives, we find that 7q11.23 CNV disrupt transcriptional circuits in disease-relevant pathways already at the pluripotent state. These alterations are then selectively amplified upon differentiation into disease-relevant lineages, thereby establishing the value of large iPSC cohorts in the elucidation of disease-relevant developmental pathways. In addition, we functionally define the quota of transcriptional dysregulation specifically caused by dosage imbalances in GTF2I (also known as TFII-I), a transcription factor in 7q11.23 thought to play a critical role in the two conditions, which we found associated to key repressive chromatin modifiers. Finally, we created an open-access web-based platform (accessible at http://bio.ieo.eu/wbs/ ) to make accessible our multi-layered datasets and integrate contributions by the entire community working on the molecular dissection of the 7q11.23 syndromes. Overall design: We reprogrammed skin fibroblasts from patients harbouring a 7q11.23 hemi-deletion (WBS, 4 patients; +1 atypical deletion, AtWBS) or microduplication (7dupASD; 2 patients), as well as from one unaffected relative and two unrelated controls, using integration-free mRNA-reprogramming, leading to the establishment of a total of 27 characterized iPSC clones. We profiled these by RNAseq (either polyA or ribo-zero). To isolate the contribution of GTF2I to the transcriptional dysregulation, we created stable lines expressing a short hairpin against GTF2I from a representative subset of these iPSC clones, and profiled by RNAseq 7 such lines along with their respective scramble controls. Finally, we also profiled by RNAseq mesenchymal stem cells (MSC) derived from a representative subset of the lines.
Publication Title
RNAontheBENCH: computational and empirical resources for benchmarking RNAseq quantification and differential expression methods.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 6 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Onconase represents a new class of RNA-damaging drugs. Mechanistically, Onconase is thought to internalize, where it degrades intracellular RNAs such as tRNA and double-stranded RNA, and thereby suppresses protein synthesis. However, there may be additional or alternative mechanism(s) of action.
Publication Title
Onconase responsive genes in human mesothelioma cells: implications for an RNA damaging therapeutic agent.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Role of CD34 antigen in myeloid differentiation of human hematopoietic progenitor cells.
Sample Metadata Fields
No sample metadata fields
View Samples
GSE8003- Homo sapiens
- 3 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
In order to investigate the role of CD34 antigen in haematopoietic commitment, we overexpressed the human CD34 cDNA in human CD34+ cells by retroviral gene transfer.
Publication Title
Role of CD34 antigen in myeloid differentiation of human hematopoietic progenitor cells.
Sample Metadata Fields
No sample metadata fields
View Samples GSE8002- Homo sapiens
- 3 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
In order to investigate the role of CD34 antigen in haematopoietic commitment, we silenced the CD34 gene expression in CD34+ stem/progenitor cells using a siRNA approach.
Publication Title
Role of CD34 antigen in myeloid differentiation of human hematopoietic progenitor cells.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus, Homo sapiens
- 66 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The TLX1 and TLX3 transcription factor oncogenes play an important role in the pathogenesis of T-cell acute lymphoblastic leukemia (T-ALL)1,2. Here we used reverse engineering of global transcriptional networks to decipher the oncogenic regulatory circuit controlled by TLX1 and TLX3. This Systems Biology analysis defined TLX1 and TLX3 as master regulators of an oncogenic transcriptional circuit governing T-ALL. Notably, network structure analysis of this hierarchical network identified RUNX1 as an important mediator of TLX1 and TLX3 induced T-ALL, and predicted a tumor suppressor role for RUNX1 in T-cell transformation. Consistent with these results, we identified recurrent somatic loss of function mutations in RUNX1 in human T-ALL. Overall, these results place TLX1 and TLX3 atop of an oncogenic transcriptional network controlling leukemia development, demonstrate power of network analysis to identify key elements in the regulatory circuits governing human cancer and identify RUNX1 as a tumor suppressor gene in T-ALL.
Publication Title
Disregulated expression of the transcription factor ThPOK during T-cell development leads to high incidence of T-cell lymphomas.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Mus musculus
- 59 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Transgenic expression of key transcritpion factors inducing T-cell leukemias in mice.
Publication Title
Disregulated expression of the transcription factor ThPOK during T-cell development leads to high incidence of T-cell lymphomas.
Sample Metadata Fields
Specimen part
View Samples- Oryza sativa indica group
- 23 Downloadable Samples
- Affymetrix Rice Genome Array (rice)
Description
Analysis of root gene expression of salt-tolerant genotypes FL478, Pokkali and IR63731, and salt-sensitive genotype IR29 under control and salinity-stressed conditions during vegetative growth. Results provide insight into the genetic basis of salt tolerance in indica rice.
Publication Title
Root-specific transcript profiling of contrasting rice genotypes in response to salinity stress.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 18 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
The histone methyltransferase Wbp7 controls macrophage function through GPI glycolipid anchor synthesis.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Mus musculus
- 18 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Histone methyltransferases catalyze site-specific deposition of methyl groups, enabling recruitment of transcriptional regulators. In mammals, trimethylation of lysine 4 in histone H3, a modification localized at the transcription start sites of active genes, is catalyzed by six enzymes (SET1a and SET1b, MLL1MLL4) whose specific functions are largely unknown. By using a genomic approach, we found that in macrophages, MLL4 (also known as Wbp7) was required for the expression of Pigp, an essential component of the GPI-GlcNAc transferase, the enzyme catalyzing the first step of glycosylphosphatidylinositol (GPI) anchor synthesis. Impaired Pigp expression in Wbp7-/- macrophages abolished GPI anchor-dependent loading of proteins on the cell membrane. Consistently, loss of GPI-anchored CD14, the coreceptor for lipopolysaccharide (LPS)
Publication Title
The histone methyltransferase Wbp7 controls macrophage function through GPI glycolipid anchor synthesis.
Sample Metadata Fields
Specimen part, Treatment
View Samples