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SRP123625
Mus musculus
6 Downloadable Samples
Illumina HiSeq 2500
Description
Somatic ribosomal protein defects have recently been described in cancer, yet their impact on cellular transcription and translation remain poorly understood. Here we integrated mRNA sequencing, ribosome footprinting, polysomal RNA seq and quantitative mass spectrometry datasets obtained from an isogenic mouse lymphoid cell model in order to study the T-cell acute lymphoblastic leukemia (T-ALL) associated R98S mutation in ribosomal protein L10 (RPL10 R98S). RPL10 R98S induced changes in protein levels were to a much larger extent caused by transcriptional then translational changes and RPL10 R98S cells showed a gene signature corresponding to deregulation of hematopoietic transcription factors. Phosphoserine phosphatase (PSPH), a key enzyme in serine biosynthesis, displayed elevated transcription and translation and was one of the proteins showing the strongest upregulation in RPL10 R98S cells. Increased Psph protein levels were confirmed in RPL10 R98S engineered JURKAT cells and in hematopoietic cell cultures derived from Rpl10 R98S knock-in mice. Moreover, elevated serine and glycine biosynthesis in RPL10 R98S cells was supported by metabolic flux analyses. Analysis of PSPH expression levels in T-ALL patient samples revealed that PSPH upregulation is a generalized phenomenon in this disease, associated with elevated circulating serine and glycine levels. Addition of serine and glycine enhanced survival of stromal and myeloid cells, suggesting supportive effects on the hematopoietic niche. Finally, reduction of PSPH expression levels in T-ALL cell lines suppressed their in vitro proliferation and their capacity to expand in T-ALL xenograft models. In conclusion, transcriptome, translatome and proteome analysis of the RPL10 R98S mutation identified RPL10 R98S driven induction of cellular serine biosynthesis. Whereas serine metabolism has been implicated in cancer via PHGDH amplification, this is the first report supporting dependence of ALL cells on the serine biosynthesis enzyme PSPH. Overall design: 3 biological replicates for each condition (RPL10 R98S, RPL10 WT)
Publication Title
Translatome analysis reveals altered serine and glycine metabolism in T-cell acute lymphoblastic leukemia cells.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 27 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
An evaluation of biopsies from patients with in-transit extremity melanoma who have been treated with ADH-1 followed by melphalan in the setting of isolated limb infusion
Publication Title
Prospective multicenter phase II trial of systemic ADH-1 in combination with melphalan via isolated limb infusion in patients with advanced extremity melanoma.
Sample Metadata Fields
Disease, Disease stage, Treatment
View Samples- Drosophila melanogaster
- 6 Downloadable Samples
- Affymetrix Drosophila Genome 2.0 Array (drosophila2)
Description
The microbial population that live within the gut of animals influences their physiology. We used axenic and recolonized flies to identify genes whose expression is modulated by the presence of a bacterial flora in the gut.
Publication Title
Drosophila microbiota modulates host metabolic gene expression via IMD/NF-κB signaling.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Drosophila melanogaster
- 36 Downloadable Samples
- Affymetrix Drosophila Genome 2.0 Array (drosophila2)
Description
Dentatorubral-pallidoluysian Atrophy (DRPLA) is a human polyQ disease caused by the expansion of a CAG strech in the atrophin-1 (at-1) gene. In all vertebrates, a second atrophin gene (at-2) is present and it encodes a related protein void of polyQ tracks. In D.melanogaster there is one conserved Atrophin (Atro) gene, ubiquitously expressed, which contains all functional domains of vertebrate Atrophins, including two polyQ stretches. To understand to what extent transcriptional alterations cause neurodegeneration and are linked to the normal functions of Atrophin, we performed a genome wide transcriptional profiling in our Drosophila models, focusing on primary events that precede neurodegeneration.
Publication Title
Polyglutamine Atrophin provokes neurodegeneration in Drosophila by repressing fat.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Invasion of lymphatic vessels is a key step in the metastasis of primary tumour cells to draining lymph nodes. Recent evidence indicates that such metastasis can be facilitated by tumour lymphangiogenesis, although it remains unclear whether this is a consequence of increased lymphatic vessel numbers or alteration in the properties of the vessels themselves. Here we have addressed this important question by comparing the RNA profile of normal dermal lymphatic endothelial cells (LEC) with those isolated from tumours of murine T-241/VEGF-C metastatic fibrosarcoma. Our findings reveal significant changes in the expression of some 792 genes in tumour lymphatics ( 2 fold up/downregulation, p 0.05), involving particularly transcripts associated with junctional adhesion, immunomodulation, extracellular matrix and vessel growth/patterning, several of which we have confirmed by RT-PCR and/or immunohistochemistry. Interestingly, this altered phenotype could not be attributed solely to VEGF-C induced lymphoproliferation, as no similar change in gene expression was reported when human LEC were cultured with VEGF-C in vitro. Moreover, we show that a key protein upregulated in the mouse model, namely the tight junction protein Endothelial Cell Specific Adhesion Molecule (ESAM), is similarly upregulated in tumour lymphatic vessels from 2/2 patients with head and neck squamous cell carcinoma and 4/4 patients with aggressive bladder carcinoma. These findings demonstrate a previously unrecognized influence of tumour environment on lymphatic gene expression and identify candidate tumour specific vessel markers that may prove valuable for either prognosis or therapy.
Publication Title
A novel gene expression profile in lymphatics associated with tumor growth and nodal metastasis.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 65 Downloadable Samples
- Affymetrix Human Genome U219 Array (hgu219)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Genetically Engineered iPSC-Derived FTDP-17 MAPT Neurons Display Mutation-Specific Neurodegenerative and Neurodevelopmental Phenotypes.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Homo sapiens
- 46 Downloadable Samples
- Affymetrix Human Genome U219 Array (hgu219)
Description
The development of an effective therapy against tauopathies like Alzheimers disease (AD) and frontotemporal dementia (FTD) remains challenging, partly due to limited access to fresh brain tissue, the lack of translational in vitro disease models and the fact that underlying molecular pathways remain to be deciphered. Several genes play an important role in the pathogenesis of AD and FTD, one of them being the MAPT gene encoding the microtubule-associated protein tau. Over the past few years, it has been shown that induced pluripotent stem cells (iPSC) can be used to model various human disorders and can serve as translational in vitro tools. Therefore, we generated iPSC harboring the pathogenic FTDP-17 (frontotemporal dementia and parkinsonism linked to chromosome 17) associated mutations IVS10+16 with and without P301S in MAPT using Zinc Finger Nuclease technology. Whole transcriptome analysis of MAPT IVS10+16 neurons reveals neuronal subtype differences, reduced neural progenitor proliferation potential and aberrant WNT signaling. Notably, all phenotypes were recapitulated using patient-derived neurons. Finally, an additional P301S mutation causes an increased calcium bursting frequency, reduced lysosomal acidity and tau oligomerization.
Publication Title
Genetically Engineered iPSC-Derived FTDP-17 MAPT Neurons Display Mutation-Specific Neurodegenerative and Neurodevelopmental Phenotypes.
Sample Metadata Fields
Treatment
View Samples- Homo sapiens
- 23 Downloadable Samples
- Affymetrix Human Genome U219 Array (hgu219)
Description
The development of an effective therapy against tauopathies like Alzheimers disease (AD) and frontotemporal dementia (FTD) remains challenging, partly due to limited access to fresh brain tissue, the lack of translational in vitro disease models and the fact that underlying molecular pathways remain to be deciphered. Several genes play an important role in the pathogenesis of AD and FTD, one of them being the MAPT gene encoding the microtubule-associated protein tau. Over the past few years, it has been shown that induced pluripotent stem cells (iPSC) can be used to model various human disorders and can serve as translational in vitro tools. Therefore, we generated iPSC harboring the pathogenic FTDP-17 (frontotemporal dementia and parkinsonism linked to chromosome 17) associated mutations IVS10+16 with and without P301S in MAPT using Zinc Finger Nuclease technology. Whole transcriptome analysis of MAPT IVS10+16 neurons reveals neuronal subtype differences, reduced neural progenitor proliferation potential and aberrant WNT signaling. Notably, all phenotypes were recapitulated using patient-derived neurons. Finally, an additional P301S mutation causes an increased calcium bursting frequency, reduced lysosomal acidity and tau oligomerization.
Publication Title
Genetically Engineered iPSC-Derived FTDP-17 MAPT Neurons Display Mutation-Specific Neurodegenerative and Neurodevelopmental Phenotypes.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Homo sapiens
- 42 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
Identification of genes and pathways relevant to Cervical cancer pathogenesis. The study also aimed at identifying probable mechanistic differences in the low and high HOTAIR expressing cervical cancers patients .
Publication Title
Bridging Links between Long Noncoding RNA HOTAIR and HPV Oncoprotein E7 in Cervical Cancer Pathogenesis.
Sample Metadata Fields
Age, Specimen part
View Samples- Homo sapiens
- 30 Downloadable Samples
- Affymetrix Human Transcriptome Array 2.0 (hta20)
Description
In this dataset, we included expression data obtained from 30 resected human PDAC tumors, to examine what genes are differentially expressed in different cohorts that might lead to various outcomes
Publication Title
Identification of unique neoantigen qualities in long-term survivors of pancreatic cancer.
Sample Metadata Fields
Specimen part
View Samples