Drought tolerance is a key trait for increasing and stabilizing barley productivity in dry areas worldwide. Identification of the genes responsible for drought tolerance in barley (Hordeum vulgare L.) will facilitate understanding of the molecular mechanisms of drought tolerance, and also genetic improvement of barley through marker-assisted selection or gene transformation. To monitor the changes in gene expression at transcription levels in barley leaves during the reproductive stage under drought conditions, the 22K Affymetrix Barley 1 microarray was used to screen two drought-tolerant barley genotypes, Martin and Hordeum spontaneum 41-1 (HS41-1), and one drought-sensitive genotype Moroc9-75. Seventeen genes were expressed exclusively in the two drought-tolerant genotypes under drought stress, and their encoded proteins may play significant roles in enhancing drought tolerance through controlling stomatal closure via carbon metabolism (NADP malic enzyme (NADP-ME) and pyruvate dehydrogenase (PDH), synthesizing the osmoprotectant glycine-betaine (C-4 sterol methyl oxidase (CSMO), generating protectants against reactive-oxygen-species scavenging (aldehyde dehydrogenase (ALDH), ascorbate-dependant oxidoreductase (ADOR), and stabilizing membranes and proteins (heat-shock protein 17.8 (HSP17.8) and dehydrin 3 (DHN3). Moreover, 17 genes were abundantly expressed in Martin and HS41-1 compared with Moroc9-75 under both drought and control conditions. These genes were likely constitutively expressed in drought-tolerant genotypes. Among them, 7 known annotated genes might enhance drought tolerance through signaling (such as calcium-dependent protein kinase (CDPK) and membrane steroid binding protein (MSBP), anti-senescence (G2 pea dark accumulated protein GDA2) and detoxification (glutathione S-transferase (GST) pathways. In addition, 18 genes, including those encoding l-pyrroline-5-carboxylate synthetase (P5CS), protein phosphatase 2C-like protein (PP2C) and several chaperones, were differentially expressed in all genotypes under drought; thus, they were more likely general drought-responsive genes in barley. These results could provide new insights into further understanding of drought-tolerance mechanisms in barley.
Differentially expressed genes between drought-tolerant and drought-sensitive barley genotypes in response to drought stress during the reproductive stage.
Specimen part, Treatment
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Polarization of the effects of autoimmune and neurodegenerative risk alleles in leukocytes.
Sex, Age, Specimen part
View SamplesGene expression profiling of CD4 T-Cells (CD4+CD62L+) from human peripheral blood mononuclear cells (PBMCs). PBMCs were isolated from healthy individuals from the Boston area.
Polarization of the effects of autoimmune and neurodegenerative risk alleles in leukocytes.
Sex, Age, Specimen part
View SamplesGene expression profiling of Monocytes (CD14+CD16-) from human peripheral blood mononuclear cells (PBMCs). PBMCs were isolated from healthy individuals from the Boston area.
Polarization of the effects of autoimmune and neurodegenerative risk alleles in leukocytes.
Sex, Specimen part
View SamplesIn several developmental lineages, an increase in expression of the MYC proto-oncogene drives the transition from quiescent stem cells to transit amplifying cells. The mechanism by which MYC restricts self-renewal of adult stem cells is unknown. Here, we show that MYC activates a stereotypic transcriptional program of genes involved in protein translation and mitochondrial biogenesis in mammary epithelial cells and indirectly inhibits the YAP/TAZ co-activators that are essential for mammary stem cell self-renewal. We identify a phospholipase of the mitochondrial outer membrane, PLD6, as the mediator of MYC activity. PLD6 mediates a change in the mitochondrial fusion/fission balance that promotes nuclear export of YAP/TAZ in a LATS- and RHO-independent manner. Mouse models and human pathological data confirm that MYC suppresses YAP/TAZ activity in mammary tumors. PLD6 is also required for glutaminolysis, arguing that MYC-dependent changes in mitochondrial dynamics balance cellular energy metabolism with the self-renewal potential of adult stem cells. Overall design: RNA-Seq Experiments in 2 different primary breast epithelial cell lines (HMLE, which were sorted according to CD44/CD24 surface markers & unsorted IMEC). Both cell lines expressed a doxycycline-inducible version of MYC. For the HMLE cell line DGE analysis was performed for the uninduced (EtOH) situation, comparing CD44high vs CD44 low and for the induced situation Dox vs. EtOH for the CD44high population. For the IMEC cell line DGE was performed by comparing Dox-treated populations expressing either Dox-inducible MYC or a vector control which allows to filter out potential effects due to doxycycline treatment.
A MYC-Driven Change in Mitochondrial Dynamics Limits YAP/TAZ Function in Mammary Epithelial Cells and Breast Cancer.
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View SamplesEmbryonal Tumors with Multilayered Rosettes (ETMRs) have recently been described as a new entity of rare pediatric brain tumors with fatal outcome. We show here that ETMRs are characterized by a parallel activation of Shh- and Wnt-signaling. Co-activation of these pathways in murine neural precursors is sufficient to induce ETMR-like tumors in vivo that resemble their human counterparts based on histology and global gene expression analyses, and point to apical radial glia cells as the possible tumor cell-of-origin. Overexpression of LIN28A, which is a hallmark of human ETMRs, augments Sonic Hedgehog (Shh)- and Wnt-signaling in these precursor cells through downregulation of let7-miRNA, and LIN28A/let7a interaction with the Shh-pathway was detected at the level of Gli mRNA. Finally, human ETMR cells that were transplanted into immunocompromised host mice were responsive to the Shh-inhibitor Arsenic trioxide (ATO). Our findings provide a novel mouse model to study this tumor type, demonstrate the driving role of Wnt- and Shh-activation in the growth of ETMRs and propose downstream inhibition of Shh-signaling as a therapeutic option for patients with ETMRs.
A mouse model for embryonal tumors with multilayered rosettes uncovers the therapeutic potential of Sonic-hedgehog inhibitors.
Specimen part
View SamplesEpendymal tumors across age groups have been classified and graded solely by histopathology. It is, however, commonly accepted that this classification scheme has limited clinical utility based on its lack of reproducibility in predicting patient outcome. We aimed at establishing a reliable molecular classification using DNA methylation fingerprints and gene expression data of the tumors on a large cohort of 500 tumors. Nine robust molecular subgroups, three in each anatomic compartment of the central nervous system (CNS), were identified.
Molecular Classification of Ependymal Tumors across All CNS Compartments, Histopathological Grades, and Age Groups.
Sex, Specimen part
View SamplesGene expression (mRNA) profiling of human ependymomas
Delineation of two clinically and molecularly distinct subgroups of posterior fossa ependymoma.
Sex, Age, Specimen part
View SamplesPediatric high-grade gliomas (pHGGs) harboring the K27M mutation of H3F3A (histone H3.3) are characterized by global reduction of the repressive histone mark H3K27me3 and DNA hypomethylation.
Reduced H3K27me3 and DNA hypomethylation are major drivers of gene expression in K27M mutant pediatric high-grade gliomas.
Sex, Age, Disease, Disease stage
View SamplesAtypical teratoid/rhabdoid tumor (ATRT) is one of the most common brain tumors in infants. Although the prognosis of ATRT patients is poor, some patients respond favorably to current treatments, suggesting molecular inter-tumor heterogeneity. To investigate this further, we genetically and epigenetically analyzed a large series of human ATRTs. Three distinct molecular subgroups of ATRTs, associated with differences in demographics, tumor location, and type of SMARCB1 alterations, were identified. Whole-genome DNA and RNA sequencing found no recurrent mutations in addition to SMARCB1 that would explain the differences between subgroups. Whole-genome bisulfite sequencing and H3K27Ac chromatin-immunoprecipitation sequencing of primary tumors, however, revealed clear differences, leading to the identification of subgroup-specific regulatory networks and potential therapeutic targets.
Atypical Teratoid/Rhabdoid Tumors Are Comprised of Three Epigenetic Subgroups with Distinct Enhancer Landscapes.
Sex, Age
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