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SRP200805
Homo sapiens
6 Downloadable Samples
Illumina HiSeq 4000
Description
Connections between RNA polymerase II (RNAPII) transcription stress, R-loops, and genome instability have been established however, the underlying mechanisms remain poorly understood. Here we used a mutant version of elongation factor TFIIS (TFIISmut) to specifically induce increased levels of RNAPII pausing, arrest, and/or backtracking in human cells. TFIISmut expression results in slower elongation rates, relative depletion of polymerases from the end of genes, and increased levels of stopped RNAPII. It affects mRNA splicing and termination as well. Remarkably, however, TFIISmut expression also dramatically increases R-loops, which may form at the anterior end of backtracked RNAPII and trigger genome instability, including DNA strand breaks. These results shed new light on the relationship between transcription stress and R-loops, and suggest that different classes of R-loops exist, potentially with distinct consequences for genome instability. Overall design: To study RNAPII backtracking and its effects in human cells, we used HEK293 TREX cells in which we overexpressed, under the control of a dox-promoter, a dominant negative form of TFIIS (TFIIS mut), an elongation factor necessary for stimulating RNAPII intrinsic cleavage activity. TFIISmut cells were maintained in the presence of Dox to ensure over-expression for 48 hours prior to harvest..
Publication Title
Elongation Factor TFIIS Prevents Transcription Stress and R-Loop Accumulation to Maintain Genome Stability.
Sample Metadata Fields
Cell line, Treatment, Subject
View Samples- Homo sapiens
- 8 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Glioblastoma (GBM) is the most devastating tumour of the brain, endowed with a fatal prognosis. Indeed, the complete eradication of cancer cell disseminated outside the GBM mass still remains a crucial issue. Given the reported strong association existing between Annexin 2A (ANXA2) expression and cell dissemination in many cancers, we evaluated the effects exerted by the modulation of ANXA2 levels in GBM cells and assessed its potential in predicting patient outcome. Here, we show that expression of ANXA2 positively correlates with metastatic gene signatures and demonstrates to be prognostic by itself. Indeed, we prove that ANXA2 is involved in cell migration, invasion, cytoskeletal remodeling and proliferation in GBM cells. Moreover, we were able to construct a gene signature representative of ANXA2 inhibition, which showed a significant prognostic potential in different GBM patient cohorts.
Publication Title
Annexin 2A sustains glioblastoma cell dissemination and proliferation.
Sample Metadata Fields
Specimen part
View Samples- Oryza sativa
- 12 Downloadable Samples
- Affymetrix Rice Genome Array (rice)
Description
Transgenic rice plants expressing isopentenyltransferase (IPT), an enzyme that catalyzes the rate-limiting step in CK synthesis under the control of SARK, a maturation- and stress-inducible promoter. Increased CK production resulted in sink source alteration and enhanced drought tolerance of the transgenic plants.
Publication Title
Cytokinin-mediated source/sink modifications improve drought tolerance and increase grain yield in rice under water-stress.
Sample Metadata Fields
Age, Specimen part
View Samples- Mus musculus
- 6 Downloadable Samples
- Illumina HiSeq 2000, NextSeq 500
Description
Cell proliferation is essential to rapid tissue growth and repair, but is inherently associated with considerable genome damage that cells must efficiently prevent or fix to prevent cell cycle arrest. Here, we implicate the transcription factor Gata6 in regulation of adult mouse hair follicle regeneration where it controls the renewal of the rapidly proliferating epithelial (matrix) progenitors and hence the extent of production of terminally differentiated lineages. We find that Gata6 protects against DNA damage associated with proliferation, thus preventing cell cycle arrest and apoptosis. Furthermore, we show that Gata6 stimulates the Eddarad/NF-kB pathway, important for DNA-damage repair and stress response in general, and for hair follicle growth in particular. Finally, we find Edaradd essential, downstream of Gata6 for cell survival and proliferation. Our data add to recent evidence in embryonic stem and neural progenitor cells, suggesting a model whereby developmentally regulated transcription factors protect from DNA damage associated with proliferation occurring at key stages of rapid tissue growth. Our data may aid in understanding why Gata6 is a frequent target of amplification in cancers. Overall design: Gene expression profiling by mRNA-seq to identify differentially expressed genes in wild type (WT) and Gata6 induced knockout (iKO) mouse epidermal keratinocytes
Publication Title
Gata6 promotes hair follicle progenitor cell renewal by genome maintenance during proliferation.
Sample Metadata Fields
Treatment, Subject
View Samples- Arabidopsis thaliana
- 24 Downloadable Samples
- Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)
Description
Metal oxide engineered nanoparticles, which are widely used in diverse applications, are known to impact terrestrial plants. These nanoparticles have a potential to induce changes in plant tissue transcriptomes, and thereby the productivity. Here we looked at how the two commonly used nanoparticles, nano-titania (TiO2) and nano-ceria (CeO2) can impact the underlying mechanisms associated plant growth at genome level.
Publication Title
Molecular and physiological responses to titanium dioxide and cerium oxide nanoparticles in Arabidopsis.
Sample Metadata Fields
Age, Specimen part
View Samples- Arabidopsis thaliana
- 12 Downloadable Samples
- Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)
Description
Seed germination of a terrestrial plant constitute dynamic changes in various physiological processes related to growth and development. These physiological processes can be affected by various abiotic and biotic stressors. Here we looked at how the two commonly used nanoparticles, nano-titania (TiO2) and nano-ceria (CeO2) can impact the underlying mechanisms associated with germination at genome level.
Publication Title
Phenotypic and genomic responses to titanium dioxide and cerium oxide nanoparticles in Arabidopsis germinants.
Sample Metadata Fields
Age, Specimen part, Treatment
View Samples- Mus musculus
- 18 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
In homeostasis of adult vertebrate tissues, stem cells are thought to self-renew by infrequent and asymmetric divisions that generate another stem cell daughter and a progenitor daughter cell committed to differentiate. This model is based largely on in vivo invertebrate or in vitro mammal studies. Here we examine the dynamic behaviour of adult hair follicle stem cells in their normal setting by employing mice with repressible H2B-GFP expression to track cell divisions and Cre inducible mice to perform long-term single cell lineage tracing. We provide direct evidence for the infrequent stem cell division model in intact tissue. Moreover, we find that differentiation of progenitor cells occurs at different times and tissue locations than self-renewal of stem cells. Distinct fates of differentiation or self-renewal are assigned to individual cells in a temporal-spatial manner. We propose that large clusters of tissue stem cells behave as populations, whose maintenance involves unidirectional daughter-cell fate decisions.
Publication Title
Distinct self-renewal and differentiation phases in the niche of infrequently dividing hair follicle stem cells.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 51 Downloadable Samples
- Affymetrix Human Genome U95 Version 2 Array (hgu95av2)
Description
Time-course and concentration-effect experiments with multiple time points and drug concentrations provide far more valuable information than experiments with just two design-points (treated vs. control), as commonly performed in most microarray studies. Analysis of the data from such complex experiments, however, remains a challenge. Here we present a semi-automated method for fitting time profiles and concentration-effect patterns, simultaneously, to gene expression data. The submodels for time-course included exponential increase and decrease models with parameters such as initial expression level, maximum effect, and rate-constant (or half-time). The submodel for concentration-effect was a 4-parameter Hill model.
Publication Title
Simultaneous modeling of concentration-effect and time-course patterns in gene expression data from microarrays.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 8 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Quiescent hair follicle (HF) bulge stem cells (SCs) differentiate to early progenitor (EP) hair germ (HG) cells, which divide to produce transit-amplifying (TA) matrix cells. EPs can revert to SCs upon injury, but whether this de-differentiation occurs in normal HF homeostasis (hair cycle), and the mechanisms regulating both differentiation and de-differentiation are unclear. Here we use lineage tracing, gain of function, transcriptional profiling, and functional assays to examine the role of observed endogenous Runx1 level changes in the hair cycle. We find that forced Runx1 expression implements hair degeneration (catagen) and simultaneously promotes changes in the quiescent bulge SC transcriptome towards a cell-state resembling the EP HG fate. This cell-state transition is functionally reversible. We propose that SC differentiation and de-differentiation are likely to occur during normal HF degeneration and niche restructuring in response to changes in endogenous Runx1 levels associated with SC location with respect to the niche.
Publication Title
High Runx1 levels promote a reversible, more-differentiated cell state in hair-follicle stem cells during quiescence.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
effect of over-expression LIGHT on T cells for the liver gene expression
Publication Title
Lymphotoxin beta receptor-dependent control of lipid homeostasis.
Sample Metadata Fields
No sample metadata fields
View Samples