Transcriptional profiling of guard cells and mesophyll cells in response to ABA treatment
Isolation of a strong Arabidopsis guard cell promoter and its potential as a research tool.
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Specimen part, Disease, Disease stage, Compound
View SamplesWe evaluated how different microbial species commonly associated with laboratory-reared Drosophila melanogaster impact host biology at the level of gene expression in the dissected adult gut or the entire adult organism. We observed that guts from gnotobiotic animals associated from the embryonic stage with either zero, one or three bacterial species demonstrated indistinguishable transcriptional profiles. Additionally, we found that the gut transcriptional profiles of animals reared in the presence of the yeast Saccharomyces cerevisiae alone or in combination with bacteria could recapitulate those of conventionally-reared animals. In contrast, we found whole body transcriptional profiles of conventionally-reared animals were distinct from all of the gnotobiotic treatments tested. Our data suggest that adult flies are insensitive to the ingestion of different bacterial species but that prior to adulthood, different microbes impact the host in ways that lead to global transcriptional differences observable across the whole adult body.
No associated publication
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Sex, Age, Specimen part, Disease, Cell line, Treatment
View SamplesMasseter and Tibialis anterior muscles from adult female control mice to determine expression differences between muscle groups
Expression profiling reveals heightened apoptosis and supports fiber size economy in the murine muscles of mastication.
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Sex, Age, Specimen part
View SamplesGene expression activity is heterogeneous in a population of isogenic cells. Identifying the molecular basis of this variability will improve our understanding of phenomena like tumor resistance to drugs, virus infection or cell fate choice. The complexity of the molecular steps and machines involved in transcription and translation could introduce sources of randomness at many levels, but a common constraint to most of these processes is its energy dependence. In eukaryotic cells most of this energy is provided by mitochondria. A clonal population of cells may show a large variability in the number and functionality of mitochondria. Cell-to-cell differences in mitochondrial content, probably originated by asymmetric segregation at cell division, contribute to heterogeneity in gene products.
No associated publication
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Sex, Specimen part, Cell line, Treatment
View SamplesTemozolomide (TMZ) is a frequently used chemotherapy for glioma; however, chemoresistance is a major problem limiting its effectiveness. Thus knowledge of mechanisms underlying this outcome could improve patient prognosis. Here, we report that deletion of a regulatory element in the HOTAIR locus increases glioma cell sensitivity to TMZ and alters transcription of multiple genes. Analysis of a combination of RNA-seq, Capture HiC and patient survival data suggests that CALCOCO1 and ZC3H10 are target genes repressed by the HOTAIR regulatory element and that both function in regulating glioma cell sensitivity to TMZ. Rescue experiments and TAD analysis based on HiC data confirmed this hypothesis. We propose a new regulatory mechanism governing glioma cell TMZ sensitivity.
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View SamplesOpen chromatin is induced locally during the repair of DNA double strand breaks, when a cascade of protein recruitments and modifications is triggered. This "ATM cascade" includes components like the Mrn complex, ATM kinase, phosphorylated histon variant ?H2AX, MDC1, E3 ligases RNF 8 and RNF8, 53BP1, and Rif1. Recent investigations have shown that also the Mad2l2 protein is a downstream effector of the ATM cascade during DNA repair. It was first described as an accessory subunit during translesion DNA repair, and more recently as a key factor inhibiting the resection of DNA 5`ends, thus promoting non-homologous end joining, and repressing homologous recombination.Naive embryonic stem cells (ESCs) have a globally open chromatin. A preliminary study from this laboratory has demonstrated that ESCs require the presence of the Mad2l2 protein for the maintenance of their transcriptional and epigenetic profiles, and thus for the stability of pluripotency (Pirouz et al., Cell Cycle 14, 1596, 2015). The aim of the present study was to correlate Mad2l2 with the ATM cascade and the chromatin status in ESCs.
No associated publication
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Sex, Specimen part, Cell line
View SamplesPediatric acute lymphoblastic leukemia (ALL) contains cytogenetically distinct subtypes that respond differently to cytotoxic drugs. Subtype classification can be also achieved through gene expression profiling. However, how to apply such classifiers to a single patient and correctly diagnose the disease subtype in an independent patient group has not been addressed. Furthermore, the underlying regulatory mechanisms responsible for the subtype-specific gene expression patterns are still largely unknown. Here, by combining three published microarray datasets (PMIDs: 12086872, 12730115, 17002788) on 535 Caucasian samples and generating a new dataset on 100 Chinese children ALL samples, we were able to 1) identify a 62-gene classifier with 97.6% accuracy from the Caucasian samples and validated it on the completely independent set of 100 Chinese samples, 2) to uncover potential regulatory networks of ALL subtypes. The classifier we identified was so far the only one that could be applied directly to a single sample and sustained validation in a large independent patient group. Our results also suggest that the etiology of ALL is largely the same among different ethnic groups, and that the transcription factor hubs in the predicted regulatory network might play important roles in regulating gene expression and development of ALL.
Gene expression-based classification and regulatory networks of pediatric acute lymphoblastic leukemia.
Specimen part, Disease, Race
View SamplesNuclear reprogramming is an inefficient process with only a small proportion of cells successful converting into induced pluripotent stem (iPS) cells. However, in order to molecularly understand the process these rare intermediates need to be identified and isolated for profiling. In the context of this project we purified the rare reprogramming for three cell types (Fibroblasts, Neutrophils and Keratinocytes) by fluorescent activated cell sorting and submitted them, together with the resulting iPS cells, to RNA sequencing.
No associated publication
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Sex, Age, Specimen part, Cell line
View SamplesThe isolation of pure populations of mouse intestinal stem cells (ISCs) is essential to facilitate functional studies of tissue homeostasis, tissue regeneration and intestinal diseases. However, the purification of ISCs has relied predominantly on the use of transgenic reporter alleles in mice. Here, we introduce a new combinational cell surface marker mediated strategy that allows the isolation of an ISC population transcriptionally and functionally equivalent to the gold standard Lgr5-GFP ISCs. We tested the ability of three cell surface marker mediated isolated strategies (termed SM2, SM4 and SM6 according to the number of key cell surface markers used) to purify ISCs and transcriptionally compared them to established standards, Lgr5-GFP high cells and cells negative for any ISC markers (Negative). The best cell surface marker mediated strategy (SM6) allowed the isolation of ISCs from reporter free mice (SM6-WT) that were functionally and transcriptionally distinct from cells isolated from transgenic mice (SM6-TG) due to Lgr5 haploinsufficiency. Overall design: To adequately benchmark the quality of our method with the existing methods, we performed first RNA sequencing with the Lgr5-GFP strain (C57/Bl6 background) on 5 FACS purified groups: SM2, SM4, SM6, Lgr5-GFPhigh reference population and cells negative or low for all of the cell surface markers used. We also performed RNA sequencing of SM6-TG and SM6-WT cells to investigate in detail potential transcriptional differences between them.
No associated publication
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Sex, Age, Specimen part, Cell line
View SamplesEthylene plays major roles in adaptive growth of rice plants in water-saturated soil; however, ethylene signaling in rice is largely unclear. Here, we report identification and characterization of ethylene-response mutants based on distinct ethylene-response phenotypes of dark-grown rice seedlings.
No associated publication
Specimen part, Treatment
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