The effect of the overexpression of a stabilized version of the transcription factor RELATED TO APETALA2.12 (RAP2.12) on the transcriptome of Arabidopsis rosettes was investigated. To this purpose, 4-week old rosette of wild-type and 35S:13RAP2.12 plants were compared. Samples were composed of pools of 3 plants.
Age-dependent regulation of ERF-VII transcription factor activity in Arabidopsis thaliana.
Age, Specimen part
View SamplesADHD is the most common neurobehavioral disorder in school-aged children. In addition to genetic factors, environmental influences or gene x environmental interactions also play an important role in ADHD. One example of a well studied environmental risk factor for ADHD is exposure to polychlorinated biphenyls (PCBs). In this study, we investigated whether the well-established genetic model of ADHD based on the Spontaneously Hypertensive Rat (SHR) and a well established PCB-based model of ADHD exhibited similar molecular changes in brain circuits involved in ADHD. The brains from 28 male rats (8 SHR, 8 Sprague-Dawley (SD) controls, 8 Wistar-Kyoto (WKY) controls, and 4 PCB-exposed SD rats) were harvested at postnatal day 55-65 and RNA was isolated from six brain regions of interest. The RNA was analyzed for differences in expression of a set of 308 probe sets interrogating 218 unique genes considered highly relevant to ADHD or epigenetic gene regulation using the Rat RAE 230 2.0 GeneChip (Affymetrix). Selected observations were confirmed by real time quantitative RT-PCR. The results show that the expression levels of genes Gnal, COMT, Adrbk1, Ntrk2, Hk1, Syt11 and Csnk1a1 were altered in both the SHR rats and the PCB-exposed SD rats. Arrb2, Stx12, Aqp6, Syt1, Ddc and Pgk1 expression levels were changed only in the PCB-exposed SD rats. Genes with altered expression only in the SHRs included Oprm1, Calcyon, Calmodulin, Lhx1 and Hes6.The epigenetic genes Crebbp, Mecp2 and Hdac5 are significantly altered in both models. The data provide strong evidence that genes and environment can affect different set of genes in two different models of ADHD and yet result in the similar disease-like symptoms.
A comparison of molecular alterations in environmental and genetic rat models of ADHD: a pilot study.
No sample metadata fields
View SamplesSky1 is a Saccharomyces cerevisiae rich serine-arginine (SR) protein-specific kinase and its enzymatic activity is essential in the cytotoxicity caused by cisplatin, although the molecular mechanisms supporting this function are not understood. We present a transcriptome analysis discriminating between RNA changes induced by cisplatin which are dependent or independent of the Sky1 function.
Sky1 regulates the expression of sulfur metabolism genes in response to cisplatin.
No sample metadata fields
View SamplesRNASeq data from WT, Zmym2 knockout- and Zmym2 overexpressing- E14tg2a mouse embryonic stem cells Overall design: RNASeq of ESCs in medium containing Serum and Leukaemia Inhibitory Factor (LIF)
ZMYM2 inhibits NANOG-mediated reprogramming.
Subject
View SamplesFibroblasts synthesize the extracellular matrix of connective tissue and play an essential role in maintaining tissue integrity. We have previously shown that mouse skin connective tissue, the dermis, is comprised of functionally distinct fibroblast lineages. However, the extent of fibroblast heterogeneity in human skin is unknown. Here, using a combination of spatial transcriptional profiling of human and mouse dermis and single cell transcriptional profiling of human dermal fibroblasts, we show that there are at least four distinct fibroblast populations in adult human skin. We define markers permitting prospective isolation of these cells and show that although marker expression is rapidly lost in culture, different fibroblast subpopulations retain distinct functionality in terms of Wnt signalling, T cell communication and the ability to support human epidermal reconstitution in organotypic culture. Furthermore, while some fibroblast subpopulations are spatially segregated, others are not. These findings have profound implications for normal wound healing and diseases characterized by excessive fibrosis, and suggest that ex vivo expansion or in vivo ablation of specific fibroblast subpopulations may have therapeutic applications. Overall design: Spatial RNA sequencing of human papillary versus reticular dermis for 3 individuals, and single cell RNA sequencing of dermal fibroblasts for a single individual.
Spatial and Single-Cell Transcriptional Profiling Identifies Functionally Distinct Human Dermal Fibroblast Subpopulations.
Specimen part, Subject
View SamplesKaryotypic instability, including numerical and structural chromosomal aberrations, represents a distinct feature of multiple myeloma (MM). 40-50% of patients displayed hyperdiploidy, defined by recurrent trisomies of non-random chromosomes. To characterize hyperdiploid (H) and nonhyperdiploid (NH) MM molecularly, we analyzed the gene expression profiles of 66 primary tumors, and used FISH to investigate the major chromosomal alterations. The differential expression of 225 genes mainly involved in protein biosynthesis, transcriptional machinery and oxidative phosphorylation distinguished the 28 H-MM from the 38 NH-MM cases. The 204 upregulated genes in H-MM mapped mainly to the chromosomes involved in hyperdiploidy, and the29% up-regulated genes in NH-MM mapped to 16q. The identified transcriptional fingerprint was robustly validated on a publicly available gene expression dataset of 64 MM cases; and the global expression modulation of regions on the chromosomes involved in hyperdiploidy was verified using a self-developed non-parametric statistical method. We showed that H-MM could be further divided into two distinct molecular and transcriptional entities, characterized by the presence of trisomy 11 and 1q-extracopies/chromosome 13 deletion, respectively. Our data reinforce the importance of combining molecular cytogenetics and gene expression profiling to define a genomic framework for the study of MM pathogenesis and clinical management.
Upregulation of translational machinery and distinct genetic subgroups characterise hyperdiploidy in multiple myeloma.
Sex
View SamplesTo gain insights into the molecular pathogenesis of DCM caused by LMNA mutation, a doxycycline-inducible (Dox-Off) gene expression system was used to express either a wild type (WT) or a mutant LMNA containing the pathogenic variant p.Asp300Asn (LMNAD300N) in cardiac myocytes. The LMNAD300N is associated with DCM in patients with atypical progeroid/Werner syndrome and non-syndromic cardiac progeria. Expression of the mutant LMNAD300N protein in cardiac myocytes led to severe fibrosis, apoptosis, cardiac dysfunction, and premature death. RNA-seq was performed (prior to onset of cardiac dysfunction) to identify gene signatures and transcriptional regulators responsible for this phenotype. Mechanistic studies identified activation of E2F/TP53/DDR, as a major mechanism responsible for the pathogenesis of DCM caused by the LMNAD300N mutation. Overall design: RNA-seq analysis from 2-week old WT and mice expressing mutant LMNA (LMNAD300N)
DNA Damage Response/TP53 Pathway Is Activated and Contributes to the Pathogenesis of Dilated Cardiomyopathy Associated With LMNA (Lamin A/C) Mutations.
Cell line, Subject
View SamplesExpression data from P2 mouse fibroblasts sorted for CD26, Sca1 and Dlk1. We have sorted mouse fibroblasts using the different lineages markers
Spatial and Single-Cell Transcriptional Profiling Identifies Functionally Distinct Human Dermal Fibroblast Subpopulations.
Specimen part
View SamplesThis study examined the expression profile of medullary carcioma of the colon compared to adjacent histologically normal colonic mucosa.
Medullary carcinoma of the colon: a distinct morphology reveals a distinctive immunoregulatory microenvironment.
Specimen part, Disease, Disease stage
View SamplesBackground and objective: The chromosome 13 deletion (del(13)) represents one of the most frequent chromosomal alterations in multiple myeloma (MM). del(13) is associated with an unfavorable prognosis, although there is an increasing agreement that its prognostic relevance has to be related to the ploidy status and the presence of different chromosomal translocations. This study is aimed at providing a comprehensive analysis of the transcriptional features of del(13) in MM. Design and methods: Highly purified plasma cells from 80 newly diagnosed MM patients were characterized by means of FISH and high-density oligonucleotide microarray for gene expression profiling and chromosomal alterations. Results: We identified 67 differentially expressed genes in the del(13)+ and del(13)- groups, all of which downregulated in the del(13)+ cases: 44 mapped along the whole chromosome 13, seven on chromosome 11 and three on chromosome 19. Functional analyses of the selected genes indicated their involvement in protein biosynthesis, ubiquitination and transcriptional regulation. An integrative genomic approach based on regional analyses of the gene expression data identified distinct chromosomal regions whose global expression modulation could differentiate del(13)+, in particular the upregulation of 1q21-1q42 and the downregulation of 19p and almost the entire chromosome 11. FISH analyses confirmed the close relationship between del(13)+ and the presence of extracopies of 1q21-1q42 (P=6x10-4) or the absence of chromosome 11 and 19 trisomy (P=5x10-4). Interpretation and conclusions: Our results indicate that distinct types of chromosomal aberrations are closely related to the transcriptional profiles of del(13)+, suggesting that the contribution of del(13) on the malignancy should be considered together with associated abnormalities.
Integrative genomic analysis reveals distinct transcriptional and genetic features associated with chromosome 13 deletion in multiple myeloma.
Sex
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