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SRP135885
Mus musculus
131 Downloadable Samples
Illumina HiSeq 2000
Description
Mutations in TRP53, prevalent in human cancers, reportedly drive tumorigenesis through dominant-negative-effects (DNE) over wt TRP53 and neomorphic gain-of-function (GOF) effects. We show that five TRP53 mutants do not accelerate lymphomagenesis on a TRP53-deficient background but strongly synergize with c-MYC over-expression. RNA-seq analysis revealed that mutant TRP53 does not globally repress wt TRP53 function but exerts a DNE with disproportionate impact on subsets of wt TRP53 target genes, particularly those involved in DNA repair, proliferation and metabolism. This reveals that the mutant TRP53 DNE drives tumorigenesis by modulating wt TRP53 function in a manner that is advantageous for neoplastic transformation. Overall design: Each of 5 mutant human TRP53 proteins, and a negative control, was expressed in 3 mouse lymphoma cell lines, both before and after activation of WT TRP53 with nutlin-3a.
Publication Title
Mutant TRP53 exerts a target gene-selective dominant-negative effect to drive tumor development.
Sample Metadata Fields
Cell line, Subject
View Samples- Mus musculus
- 64 Downloadable Samples
- Illumina HiSeq 1500
Description
Differentiation of haematopoietic stem cells followsa hierarchical program of transcription-factor regulated events. Early myeloid cell differentiation is dependent on PU.1 and CEBPA (CCAAT/enhancer binding protein alpha), late myeloid differentiation is orchestrated by CEBPE (CCAAT/enhancer binding protein epsilon). The influence of SWI/SNF (SWItch/Sucrose Non-Fermentable) chromatin remodelling factors as novel master regulators of haematopoietic differentiation is only beginning to be explored. Here, we identified three homozygous loss-of-function mutations in SMARCD2 (SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily d, member 2), a member of the SWI/SNF complex, in three unrelated pedigrees. We find that SMARCD2-deficient hematopoiesis results in dysfunctional neutrophil granulocytes, characterized by specific granule deficiency, myelodysplasia, and an excess of blast cells. We can show that SMARCD2 controls early steps in the differentiation of myeloid-erythroid progenitor cells in mice and zebra fish. In vitro SMARCD2 interacts with the transcription factor CEBPE. Furthermore, we find that SMARCD2 controls expression of neutrophil proteins stored in specific granules and leads to transcriptional and chromatin changes in AML cells. Hence, we identify SMARCD2 as a key factor controlling myelopoiesis and as a potential tumour suppressor in leukemia. Overall design: We analyzed CD45.2+ Lin- Mac+/low Sca1+ cKit+ (LSK) cells from Smarcd2 wild-type, heterozygous and mutant foetal livers in at least 5 replicates Additionally, we analysed three different progenitor populations from Smarcd2 wild-type and homozygous knock-out foetal livers: CD45+Lin-Sca-1-CD177+CD34lowCD16/32 (FCGR)low(MEP) CD45+Lin-Sca-1-CD177+CD34+CD16/32(FCGR)int (CMP) CD45+Lin-Sca-1-CD177+CD34+CD16/32(FCGR)high (GMP)
Publication Title
Chromatin-remodeling factor SMARCD2 regulates transcriptional networks controlling differentiation of neutrophil granulocytes.
Sample Metadata Fields
Sex, Specimen part, Cell line, Subject
View Samples- Homo sapiens
- 303 Downloadable Samples
Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
In this study gene expression profiles for 307 cases of advanced bladder cancers were compared to molecular phenotype at the tumor cell level. TUR-B tissue for RNA extraction was macrodissected from the close vicinity of the tissue sampled for immunohistochemistry to ensure high-quality sampling and to minimize the effects of intra-tumor heterogeneity. Despite excellent agreement between gene expression values and IHC-score at the single marker level, broad differences emerge when samples are clustered at the global mRNA versus tumor cell (IHC) levels. Classification at the different levels give different results in a systematic fashion, which implicates that analysis at both levels is required for optimal subtype-classification of bladder cancer.
Publication Title
Molecular classification of urothelial carcinoma: global mRNA classification versus tumour-cell phenotype classification.
Sample Metadata Fields
Specimen part
View Samples- Escherichia coli
- 4 Downloadable Samples
- Affymetrix E. coli Genome 2.0 Array (ecoli2)
Description
Dynamical response to oxygen downshift under fermentation conditions was tested by taking sample before (S1) and after (S2, S3 and S4) the oxygen downshift. The dynamical changes relevant for ongoing research on physiology were applied.
Publication Title
Norvaline is accumulated after a down-shift of oxygen in Escherichia coli W3110.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 41 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
We aimed to provide a molecular description of Lynch syndrome-associated urothelial cancer in relation to molecular subtypes of sporadic bladder cancer. Whole genome mRNA expression profiles of 41 tumors and immunohistochemical stainings against FGFR3, KRT5, CCNB1, RB1, and CDKN2A (p16) of 37 tumors from Lynch syndrome patients were generated. Pathological data, microsatellite instability, anatomic location, and overall survival data was analyzed and compared with data from sporadic bladder cancer.
Publication Title
Molecular subtype classification of urothelial carcinoma in Lynch syndrome.
Sample Metadata Fields
No sample metadata fields
View Samples- Danio rerio
- 12 Downloadable Samples
- Affymetrix Zebrafish Genome Array (zebrafish)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Estrogen receptor subtype beta2 is involved in neuromast development in zebrafish (Danio rerio) larvae.
Sample Metadata Fields
No sample metadata fields
View Samples- Bos taurus
- 12 Downloadable Samples
- Affymetrix Bovine Genome Array (bovine)
Description
Our overall objective is to identify key differences in gene expression signaling pathways in the epithelial and intralobular stromal compartments during prepartum mammary remodeling and development in the dry cow.
Publication Title
Transcriptome analysis of epithelial and stromal contributions to mammogenesis in three week prepartum cows.
Sample Metadata Fields
No sample metadata fields
View Samples- Danio rerio
- 6 Downloadable Samples
- Affymetrix Zebrafish Genome Array (zebrafish)
Description
The role of ERbeta2 in zebrafish larvae was investigated by injection of a Morpholino against ERbeta2. After 72hpf, the morphants showed a strong disruption in their sensory systems. ERbeta2 has been shown to be needed for the normal functioning of the sensory system organs, the neuromasts. The mechanisms involved in the neuromast disruption in ERbeta2 morphants was identified by microarrays gene screening. After comparison of two screening with low and hign concentration of Morpholinos, genes that were present in the two microarrays screening were selected. The genes were then chosen by relevance for the mechanisms involved in the role of ERbeta2 in neuromast development. The ngn1 transcription factor, Notch3 and Notch1a showed to be up-regulated, also confirmed by in situ hybridization. The Notch signaling is known to be involved in cell fate in developing neuromasts. The overall conclusion is that ERbeta2 by interacting with the notch signaling pathways is critical for normal development of the neuromast of the lateral line in zebrafish.
Publication Title
Estrogen receptor subtype beta2 is involved in neuromast development in zebrafish (Danio rerio) larvae.
Sample Metadata Fields
No sample metadata fields
View Samples- Danio rerio
- 6 Downloadable Samples
Affymetrix Zebrafish Genome Array (zebrafish)
Description
The role of ERbeta2 in zebrafish larvae was investigated by injection of a Morpholino against ERbeta2. After 72hpf, the morphants showed a strong disruption in their sensory systems. ERbeta2 has been shown to be needed for the normal functioning of the sensory system organs, the neuromasts. The mechanisms involved in the neuromast disruption in ERbeta2 morphants was identified by microarrays gene screening. After comparison of two screening with low and high concentration of Morpholinos, genes that were present in the two microarrays screening were selected. The genes were then chosen by relevance for the mechanisms involved in the role of ERbeta2 in neuromast development. The ngn1 transcription factor, Notch3 and Notch1a showed to be up-regulated, also confirmed by in situ hybridization. The Notch signaling is known to be involved in cell fate in developing neuromasts. The overall conclusion is that ERbeta2 by interacting with the notch signaling pathways is critical for normal development of the neuromast of the lateral line in zebrafish.
Publication Title
Estrogen receptor subtype beta2 is involved in neuromast development in zebrafish (Danio rerio) larvae.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 21 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The effects of 7.5 micromolar parthenolide (PTL) were assessed on primary CD34+ acute myelogenous leukemia specimens obtained from 12 patients.
Publication Title
Discovery of agents that eradicate leukemia stem cells using an in silico screen of public gene expression data.
Sample Metadata Fields
No sample metadata fields
View Samples