Three wheat genotypes were exposed to water stress and root tissue collected for expression analysis
Introgression of novel traits from a wild wheat relative improves drought adaptation in wheat.
Specimen part
View SamplesSpecific changes in gene expression during cancer initiation should enable discovery of biomarkers for risk assessment, early detection and targets for chemoprevention. It has been previously demonstrated that altered mRNA and proteome signatures of morphologically normal cells bearing a single inherited hit in a tumor suppressor gene parallel many changes observed in the corresponding sporadic cancer. Here, we report on the global gene expression profile of morphologically normal, cultured primary breast epithelial and stromal cells from Li-Fraumeni syndrome (LFS) TP53 mutation carriers. Our analyses identified multiple changes in gene expression in both morphologically normal breast epithelial and stromal cells associated with TP53 haploinsufficiency, as well as interlocking pathways. Notably, a dysregulated p53 signaling pathway was readily detectable. Pharmacological intervention with the p53 rescue compounds CP-31398 and PRIMA-1 provided further evidence in support of the central role of p53 in affecting these changes in LFS cells and treatment for this cancer. Because loss of signaling mediated by TP53 is associated with the development and survival of many human tumors, identification of gene expression profiles in morphologically normal cells that carry one-hit p53 mutations may reveal novel biomarkers, enabling the discovery of potential targets for chemoprevention of sporadic tumors as well.
A molecular signature of normal breast epithelial and stromal cells from Li-Fraumeni syndrome mutation carriers.
Specimen part
View SamplesPurpose: study the role of MALT1 auto-proteolysis in T cell receptor mediated activation of NF-kB. Methods: Jurkat cells were generated that express wild type MALT1, the auto-cleavage deficient MALT1-R149A mutant, the catalytic inactive MALT1-C464A mutant or the R149A-C464A double mutant (RACA). Expression of endogenous MALT1 was inactivated using TALEN technology for the Jurkat cells expressing MALT1-R149A (JDM-RA) and MALT1-C464A (JDM-CA). Illumina HISeq 2000 deep sequencing was performed to determine the mRNA profiles for MALT1, JDM-RA, JDM-CA and RACA cells in unstimulated conditions or after treatment with 75ng/ml PMA and 150 ng/ml ionomycin for 3 or 18 hrs. Results: PMA ionomycin stimulation of the MALT1 auto-cleavage defective JDM-RA cells fails to activate NF-kB-dependent transcription like for the MALT1 catalytic inactive JDM-CA cells and the double RACA mutant cells. Conclusion: MALT1 autoproteolysis is essential for transcription of NF-kB target genes Overall design: mRNA profiles of Jurkat expressing MALT1, MALT1-R149A, MALT1-C464A and MALT1-R149A-C464A after 0, 3 and 18 hours of stimulation with PMA and Ionomycin were generated by deep sequencing, in duplicate, using Illumina HISeq 2000
MALT1 auto-proteolysis is essential for NF-κB-dependent gene transcription in activated lymphocytes.
No sample metadata fields
View SamplesProper regulation of nuclear factor B (NF-B) transcriptional activity is required for normal lymphocyte function, and deregulated NF-B signaling can facilitate lymphomagenesis. We demonstrate that the API2-MALT1 fusion oncoprotein created by the recurrent t(11;18)(q21;q21) in mucosa-associated lymphoid tissue (MALT) lymphoma induces proteolytic cleavage of NF-Binducing kinase (NIK) at arginine 325. NIK cleavage requires the concerted actions of both fusion partners and generates a C-terminal NIK fragment that retains kinase activity and is resistant to proteasomal degradation. The resulting deregulated NIK activity is associated with constitutive noncanonical NF-B signaling, enhanced B cell adhesion, and apoptosis resistance. Our study reveals the gain-of-function proteolytic activity of a fusion oncoprotein and highlights the importance of the noncanonical NF-B pathway in B lymphoproliferative disease.
Cleavage of NIK by the API2-MALT1 fusion oncoprotein leads to noncanonical NF-kappaB activation.
No sample metadata fields
View SamplesComparison of t(11;18)-positive MALT lymphoma to t(11;18)-negative MALT lymphoma, with a special focus on the NF-KB pathway and it's targets
Cleavage of NIK by the API2-MALT1 fusion oncoprotein leads to noncanonical NF-kappaB activation.
Specimen part
View SamplesThe goal of this experiment was to explore the extent of KIN10 (At3g01090) transcriptional regulation and identify its early target genes in Arabidopsis mesophyll protoplasts. Results suggest that KIN10 targets a remarkably broad array of genes that orchestrate transcription networks, promote catabolism and autophagy, and suppress anabolism and ribosome biogenesis. The transient expression condition ruled out secondary or long-term effects of metabolism and growth, and circumvented experimental limitations caused by redundancy and embryonic lethality observed in mammals and plants.
A central integrator of transcription networks in plant stress and energy signalling.
No sample metadata fields
View SamplesThe goal of this experiment was to investigate the early transcript changes (6h) induced by hypoxia treatment in mesophyll protoplasts. A single pair (control & hypoxia) of GeneChips was used to confirm that hypoxia treatment altered the expression of an overlapping set of genes controlled by KIN10 (At3g01090) in Arabidopsis mesophyll protoplasts.
A central integrator of transcription networks in plant stress and energy signalling.
No sample metadata fields
View SamplesThe SnRK1 protein kinase, the plant ortholog of mammalian AMPK and yeast Snf1, is activated by the energy depletion caused by adverse environmental conditions. Upon activation, SnRK1 triggers extensive transcriptional changes to restore homeostasis and promote stress tolerance and survival partly through the inhibition of anabolism and the activation of catabolism. Despite the identification of a few bZIP transcription factors as downstream effectors, the mechanisms underlying gene regulation, and in particular gene repression by SnRK1, remain mostly unknown. microRNAs (miRNAs) are 20-24nt RNAs that regulate gene expression post-transcriptionally by driving the cleavage and/or translation attenuation of complementary mRNA targets. In addition to the well-established role of miRNAs as regulators of plant development, mounting evidence implicates miRNAs in the response to environmental stress. Given the involvement of miRNAs in stress responses and the fact that some of the SnRK1-regulated genes are miRNA targets, we postulated that miRNAs drive part of the transcriptional reprogramming triggered by SnRK1 activation. To test this we have performed comparative analyses of the transcriptional response to energy deprivation between WT and dcl1-9, a mutant deficient in miRNA biogenesis.
miRNAs mediate SnRK1-dependent energy signaling in Arabidopsis.
Specimen part, Treatment
View SamplesBecause insufficiency of the Runt-related transcription factor 2 (Runx2) limits skeletal growth, there is a great deal of effort to activate Runx2 for clinical use. In this study, we found that MS-275, the class I-specific HDAC inhibitor, activates Runx2 both transcriptionally and translationally. Therefore, we performed NGS analysis to gain accurate patterns of gene expression in mouse calvaria tissue through MS-275 administration. As a result, we could get insight that treatment of MS-275 increases genes related with osteoblast differentiation and cell proliferation, and decreases genes in field of causing apoptosis. Overall design: Mice calvarial mRNA profiles of embryonic day 17.5 wild type (WT) and Runx2+/- mice were generated by deep sequencing using Illumina NextSeq 500. Mice were administered MS-275 or vehicle. Three replicates per group.
An HDAC Inhibitor, Entinostat/MS-275, Partially Prevents Delayed Cranial Suture Closure in Heterozygous Runx2 Null Mice.
Specimen part, Treatment, Subject
View SamplesPurpose: We purified whole brain microglia of MFP2 knockout mice and control mice utilizing percoll gradient and FACS sorting, followed by microarray analysis to define the molecular changes in MFP2 knockout mice at the endstage of the disease. We compared the microglia transcriptome of Mfp2-/- microglia to that of SOD1-G93A microglia isolated from spinal cord to define the microglia signature associated with a non-neurodegenerative environment. Results and conclusions: Mfp2-/- microglia acquire an activation state characterized by activation of mammalian target of rapamycin (mTOR). In addition, activated microglia display reduced expression of genes that are normally highly expressed by surveillant microglia in steady-state conditions. The immunological profile of is heterogeneous and encompasses upregulation of both pro- and anti-inflammatory genes. In contrast to the neurodegeneration-specific microglia profile in SOD1-G93A mice, Mfp2-/- microglia do not induce genes associated with phagocytosis, lysosomal activation and neurotoxicity.
Identification of a chronic non-neurodegenerative microglia activation state in a mouse model of peroxisomal β-oxidation deficiency.
Sex, Age, Specimen part
View Samples