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GSE9452
Homo sapiens
26 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The samples are a part of a study aiming at diagnosing ulcerative colitis from genome-wide gene expression analysis of the colonic mucosa. Colonic mucosal samples were collected as endoscopic pinch biopsies from ulcerative colitis patients and from control subjects. Samples with and without macroscopic signs of inflammation were collected from the patients.
Publication Title
Diagnosis of ulcerative colitis before onset of inflammation by multivariate modeling of genome-wide gene expression data.
Sample Metadata Fields
No sample metadata fields
View Samples- Drosophila melanogaster
- 12 Downloadable Samples
- Affymetrix Drosophila Genome 2.0 Array (drosophila2)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Functional genomic analysis of the periodic transcriptome in the developing Drosophila wing.
Sample Metadata Fields
Specimen part
View Samples- Drosophila melanogaster
- 12 Downloadable Samples
Affymetrix Drosophila Genome 2.0 Array (drosophila2)
Description
The eukaryotic cell cycle, driven by both transcriptional and post-translational mechanisms, is the central molecular oscillator underlying tissue growth throughout animals. While genome-wide studies have investigated cell cycle-associated transcription in unicellular systems, global patterns of periodic transcription in multicellular tissues remain largely unexplored. Here we define the cell cycle-associated transcriptome of the developing Drosophila wing epithelium and compare it with that of cultured Drosophila S2 cells, revealing a core set of periodic genes as well as a surprising degree of context-specificity in periodic transcription. We further employ RNAi-mediated phenotypic profiling to define functional requirements for over 300 periodic genes, with a focus on those required for cell proliferation in vivo. Finally, we investigate the role of novel genes required for interkinetic nuclear migration. Combined, these findings provide a global perspective on cell cycle control in vivo, and highlight a critical need to understand the context-specific regulation of cell proliferation.
Publication Title
Functional genomic analysis of the periodic transcriptome in the developing Drosophila wing.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 12 Downloadable Samples
Illumina HiSeq 2500
Description
Tetraploidization, or genome doubling, is a prominent event in tumorigenesis, primarily because cell division in polyploid cells is error-prone and produces aneuploid cells. This study investigates changes in gene expression evoked in acute and adapted tetraploid cells and their impact on cell-cycle progression. Acute polyploidy was generated by knockdown of essential regulator of cytokinesis Anillin, which resulted in cytokinesis failure and formation of binucleate cells, or by chemical inhibition of Aurora kinases, causing abnormal mitotic exit with formation of single cells with aberrant nuclear morphology. Transcriptome analysis of these acute tetraploid cells revealed common signatures of activation of the tumor-suppressor protein p53. Suppression of proliferation in these cells was dependent on p53 and its transcriptional target - Cdk inhibitor p21. Rare proliferating tetraploid cells can emerge from acute polyploid populations. Gene expression analysis of single-cell derived, adapted tetraploid clones showed upregulation of several p53 target genes and cyclin D2, the activator of Cdk4/6/2. Overexpression of cyclin D2 in diploid cells strongly potentiated the ability to proliferate with increased DNA content despite the presence of functional p53. These results point out that p53-mediated suppression of proliferation of polyploid cells can be averted by increased levels of oncogenes such as Cyclin D2, elucidating a possible route for tetraploidy-mediated genomic instability in carcinogenesis. Overall design: Three biological replicates of cells treated with siRNA against Anillin or a non-targeting control are FACS sorted into 2N or 4N populations and assessed for gene expression differences via RNA Seq for a total of 12 samples.
Publication Title
Transcriptome analysis of tetraploid cells identifies cyclin D2 as a facilitator of adaptation to genome doubling in the presence of p53.
Sample Metadata Fields
Cell line, Subject
View Samples- Drosophila melanogaster
- 9 Downloadable Samples
- Illumina HiSeq 2500
Description
The eukaryotic cell cycle, driven by both transcriptional and post-translational mechanisms, is the central molecular oscillator underlying tissue growth throughout animals. While genome-wide studies have investigated cell cycle-associated transcription in unicellular systems, global patterns of periodic transcription in multicellular tissues remain largely unexplored. Here we define the cell cycle-associated transcriptome of the developing Drosophila wing epithelium and compare it with that of cultured Drosophila S2 cells, revealing a core set of periodic genes as well as a surprising degree of context-specificity in periodic transcription. We further employ RNAi-mediated phenotypic profiling to define functional requirements for over 300 periodic genes, with a focus on those required for cell proliferation in vivo. Finally, we investigate the role of novel genes required for interkinetic nuclear migration. Combined, these findings provide a global perspective on cell cycle control in vivo, and highlight a critical need to understand the context-specific regulation of cell proliferation. Two RNAi lines of CR32027, a non-coding RNA gene identified in this study, are examined for transcriptional changes relative to wt. Overall design: Transcriptional profiles of two RNAi knockdowns, CR32027-IR1 and CR32027-IR2, are examined in Drosophila wing pouch relative to OreR wt in triplicate by RNA Seq.
Publication Title
Functional genomic analysis of the periodic transcriptome in the developing Drosophila wing.
Sample Metadata Fields
Subject
View Samples- Danio rerio
- 24 Downloadable Samples
- IlluminaHiSeq2000
Description
Deafness due to the terminal loss of inner ear hair cells is one of the most common sensory diseases. However, non-mammalian animals (e.g. birds, amphibian and fish) regenerate damaged hair cells. In order to better understand the reasons underpinning such regeneration disparities in vertebrates, we set out to define the changes in gene expression associated with the regeneration of hair cells in the zebrafish lateral line at high resolution. We performed RNA-Seq analyses on regenerating support cells purified by fluorescence activated cell sorting (FACS). The zebrafish lateral line provides an experimentally accessible system to define the complex signaling events triggered by injury and regeneration, because these cells can be acutely killed by exposure to neomycin, after which they regenerate rapidly. Lateral line hair cells are located in the center of a mechanosensory organ known as the neuromast and are surrounded by inner support cells and an outer ring of mantle cells. Tg(sqET20) larvae express GFP strongly in mantle cells and to a lesser degree in inner support cells. We isolated GFP positive and GFP negative cells from 5 days post fertilization (dpf) Tg(sqET20) larvae at 1, 3 and 5 hours post neomycin treatment, as well as from a non-treated control. Overall design: Transgenic zebrafish Tg(sqET20) larvae at 5 days post fertilization were exposed to neomycin, dissociated, and FACS sorted into GFP positive and GFP negative populations at 1, 3, and 5 hours following treatment, along with a mock treated 1 hr control. The experiment was performed in triplicate, for a total of 24 samples.
Publication Title
Gene-expression analysis of hair cell regeneration in the zebrafish lateral line.
Sample Metadata Fields
No sample metadata fields
View Samples- Drosophila melanogaster
- 21 Downloadable Samples
- Illumina HiSeq 2000
Description
To obtain a comprehensive view of genes contributing to long-term memory we performed mRNA sequencing from single Drosophila heads following behavioral training that produces long-lasting memory. Overall design: Drosophila trained with an appetitive conditioning paradigm using Sucrose were collected prior to starvation, training, and 1 or 4 hours post-training, 5 to 6 replicates each, for RNA-Seq analysis of the fly heads with an Illumina HiSeq 2000.
Publication Title
Antimicrobial peptides modulate long-term memory.
Sample Metadata Fields
Specimen part, Subject
View Samples- Drosophila melanogaster
- 15 Downloadable Samples
- Illumina Genome Analyzer IIx
Description
Throughout Metazoa, developmental processes are controlled by a surprisingly limited number of conserved signaling pathways. Precisely how these signaling cassettes were assembled in early animal evolution remains poorly understood, as do the molecular transitions that potentiated the acquisition of their myriad developmental functions. Here we analyze the molecular evolution of the proto-oncogene YAP/Yorkie, a key effector of the Hippo signaling pathway that controls organ size in both Drosophila and mammals. Based on heterologous functional analysis of evolutionarily distant Yap/Yorkie orthologs, we demonstrate that a structurally distinct interaction interface between Yap/Yorkie and its partner TEAD/Scalloped became fixed in the eumetazoan common ancestor. We then combine transcriptional profiling of tissues expressing phylogenetically diverse forms of Yap/Yorkie with ChIP-seq validation in order to identify a common downstream gene expression program underlying the control of tissue growth in Drosophila. Intriguingly, a subset of the newly-identified Yorkie target genes are also induced by Yap in mammalian tissues, thus revealing a conserved Yap-dependent gene expression signature likely to mediate organ size control throughout bilaterian animals. Combined, these experiments provide new mechanistic insights while revealing the ancient evolutionary history of Hippo signaling. We sought to define the downstream target genes of selected Yap variants by performing RNA sequencing analysis (RNA-seq) on total RNA isolated from GMR-Gal4>Yap eye discs. Overall design: Transcriptional profiles were generated in triplicate from eye imaginal disks with either endogenous Yki, or GMR-Gal4 over-expressed Yki, Trichoplax Yap, Monosiga Yap, or Monisiga Yap+TEAD domain, using deep sequencing via Illumina Hi Seq.
Publication Title
Molecular evolution of the Yap/Yorkie proto-oncogene and elucidation of its core transcriptional program.
Sample Metadata Fields
Treatment, Subject
View Samples- Mus musculus
- 10 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
The overall goal of this project is to investigate the contribution of the inferior alveolar nerve (IAN) towards cellular mechanisms required for regeneration of the murine incisor. Here, we conducted gene expression profiling of adult murine incisor dental mesenchyme tissue following two weeks after unilateral resection of the IAN from both the denerved and contralateral incisor of five wild-type mice.
Publication Title
Secretion of shh by a neurovascular bundle niche supports mesenchymal stem cell homeostasis in the adult mouse incisor.
Sample Metadata Fields
Sex, Specimen part
View Samples- Mus musculus
- 9 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Adult-onset diseases can be associated with in utero events, but mechanisms for such temporally distant dysregulation of organ function remain unknown. The polycomb histone methyltransferase, Ezh2, stabilizes transcription by depositing repressive histone marks during development that persist into adulthood, but the function of Ezh2-mediated transcriptional stability in postnatal organ homeostasis is not understood. Here, we show that Ezh2 stabilizes the postnatal cardiac gene expression program and prevents cardiac pathology, primarily by repressing the homeodomain transcription factor Six1 in differentiating cardiac progenitors. Loss of Ezh2 in embryonic cardiac progenitors, but not in differentiated cardiomyocytes, resulted in postnatal cardiac pathology, including cardiomyocyte hypertrophy and fibrosis. Loss of Ezh2 caused broad derepression of skeletal muscle genes, including the homeodomain transcription factor Six1, which is expressed in cardiac progenitors but is normally silenced upon cardiac differentiation. Many of the deregulated genes are direct Six1 targets, implying a critical requirement for stable repression of Six1 in cardiac myocytes. Indeed, upon de-repression, Six1 promotes cardiac pathology, as it was sufficient to induce cardiac hypertrophy. Furthermore, genetic reduction of Six1 levels almost completely rescued the pathology of Ezh2-deficient hearts. Thus, repression of a single transcription factor in cardiac progenitors by Ezh2 is essential for stability of the adult heart gene expression program and homeostasis. Our results suggest that epigenetic dysregulation during discrete developmental windows can predispose to adult disease and dysregulated stress responses.
Publication Title
Epigenetic repression of cardiac progenitor gene expression by Ezh2 is required for postnatal cardiac homeostasis.
Sample Metadata Fields
Specimen part
View Samples