Remodeling of the actin cytoskeleton through actin dynamics (assembly and disassembly of filamentous actin) is known to be essential for numerous basic biological processes. In addition, recent in vitro studies provided evidence that actin dynamics participate in the control of gene expression. A spontaneous mouse mutant, corneal disease 1 (corn1), is deficient for a regulator of actin dynamics, destrin (DSTN; also known as actin depolymerizing factor or ADF), and develops epithelial hyperproliferation and neovascularization in the cornea. Dstncorn1 mice exhibit the actin dynamics defect in the corneal epithelial cells as evidenced by increased filamentous actin, offering an in vivo model to investigate the physiological significance of the transcriptional regulation by actin dynamics. To examine the effect of the Dstncorn1 mutation on gene expression, we performed a microarray analysis using the cornea from Dstncorn1 and wild-type control mice. A dramatic alteration of gene expression was observed in the Dstncorn1 cornea, with 1,226 annotated genes differentially expressed. Functional annotation of these genes revealed that most significantly enriched functional categories are associated with actin and/or cytoskeleton. Among genes that belong to these categories, a considerable number of serum response factor (SRF) target genes were found, indicating the existence of the actin-SRF pathway of transcriptional regulation in vivo. A comparative study using an allelic mutant strain, Dstncorn1-2J, with milder corneal phenotypes also suggested that the severity of the actin dynamics defect correlates with the level of gene expression changes. Our study provides evidence that actin dynamics have a strong impact on gene expression in vivo.
Effect of destrin mutations on the gene expression profile in vivo.
Sex, Age
View SamplesThe purpose of this study is to characterize gene expression changes that occur when conditional knock-out of Srf rescues mutant phenotypes in the cornea of Dstncorn1 mice.
Serum response factor: positive and negative regulation of an epithelial gene expression network in the destrin mutant cornea.
Specimen part
View SamplesTo further characterize residual undifferentiated cells after neural induction of embryonic stem cells, we performed DNA microarray analysis to identify genes expressed predominantly in residual undifferentiated cells expressing Oct4.
Dormant Pluripotent Cells Emerge during Neural Differentiation of Embryonic Stem Cells in a FoxO3-Dependent Manner.
Specimen part, Cell line
View SamplesOverexpression of high mobility group AT-hook 2 (HMGA2) associated with truncations of its 3 untranslated region (UTR) with let-7 micro RNA-complementary sequences have been identified in patients with paroxysmal nocturnal hemoglobinuria (PNH). Here, we generated transgenic mice (Hmga2 mice) with a 3UTR-trncated Hmga2 cDNA that overexpress Hmga2 mRNA and protein in hematopoietic organs. Hmga2 mice showed proliferative hematopoiesis that mimicked a myeloproliferative neoplasm (MPN)-like phenotype with increased numbers of all lineages of peripheral blood cells, hypercellular bone marrow (BM), splenomegaly with extramedullary erythropoiesis, and erythropoietin-independent erythroid colony formation compared to wild-type mice. Hmga2 BM-derived cells took over most of hematopoiesis in competitive repopulations during serial BM transplants. When we bred mice with circulating PNH cells (Piga- mice) with Hmga2 mice, the lack of GPI-linked proteins did not add an additional clonal advantage to the Hmga2+ cells. In summary, our results showed that the overexpression of a 3UTR-truncated Hmga2 leads to a proliferative hematopoiesis with clonal advantage, which may explain clonal expansion in PNH or MPN at the level of HSC.
3'UTR-truncated Hmga2 cDNA causes MPN-like hematopoiesis by conferring a clonal growth advantage at the level of HSC in mice.
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
The microRNA machinery regulates fasting-induced changes in gene expression and longevity in <i>Caenorhabditis elegans</i>.
No sample metadata fields
View SamplesIntermittent fasting (IF), a dietary restriction regimen, extends the lifespans of C. elegans and mammals by inducing gene expression changes. How fasting induces gene expression changes and longevity remains unclear. MicroRNAs (miRNAs) are small non-coding RNAs (approximately 22 nucleotides) that repress gene expression, and the expression of several miRNAs has been reported to be altered by fasting. In this study, we examined the role of the miRNA machinery in fasting-induced transcriptional changes and longevity in C. elegans. Our miRNA array analyses revealed that the expression levels of numerous miRNAs changed in adult worms after 48 hours of fasting. In addition to these changes, miRNA-mediated silencing complex (miRISC) components, including Argonaute proteins and GW182 proteins, and the miRNA-processing enzyme Drosha/DRSH-1, were up-regulated by fasting. Our lifespan measurements demonstrated that IF-induced longevity was suppressed by knockout or knockdown of miRISC components and was completely inhibited by drsh-1 ablation. Remarkably, drsh-1 ablation inhibited the fasting-induced changes in the expression of the target genes of DAF-16, the insulin/IGF-1 signaling effector. Fasting-induced transcriptome alterations were substantially and modestly suppressed in the drsh-1 null mutant and the null mutant of ain-1, a gene encoding GW182, respectively. These results indicate that components of the miRNA machinery, especially the miRNA-processing enzyme Drosha, play an important role in mediating IF-induced longevity via the regulation of fasting-induced gene expression changes.
The microRNA machinery regulates fasting-induced changes in gene expression and longevity in <i>Caenorhabditis elegans</i>.
No sample metadata fields
View SamplesTo identify the genes whose expression levels are changed before and after somatic cell reprogramming, we performed global gene expression analysis of iPS cells and their original fibrobrasts.
Structural and spatial chromatin features at developmental gene loci in human pluripotent stem cells.
Specimen part, Cell line
View SamplesWe performed the oligonucleotide microarray analysis in bipolar disorder, major depression, schizophrenia, and control subjects using postmortem prefrontal cortices provided by the Stanley Foundation Brain Collection. By comparing the gene expression profiles of similar but distinctive mental disorders, we explored the uniqueness of bipolar disorder and its similarity to other mental disorders at the molecular level. Notably, most of the altered gene expressions in each disease were not shared by one another, suggesting the molecular distinctiveness of these mental disorders. We found a tendency of downregulation of the genes encoding receptor, channels or transporters, and upregulation of the genes encoding stress response proteins or molecular chaperons in bipolar disorder. Altered expressions in bipolar disorder shared by other mental disorders mainly consisted of upregulation of the genes encoding proteins for transcription or translation. The genes identified in this study would be useful for the understanding of the pathophysiology of bipolar disorder, as well as the common pathophysiological background in major mental disorders at the molecular level.
Molecular characterization of bipolar disorder by comparing gene expression profiles of postmortem brains of major mental disorders.
No sample metadata fields
View SamplesThe gain of Protocadherin LKC (PCDH24) expression in colon carcinoma cell line HCT116 has been shown to induce contact inhibition, thereby completely abolishing tumor formation in vivo. To clarify the molecular mechanism, we performed DNA microarray analysis and compared gene-expression pattern between control and PCDH24-expressing HCT116 cells. Approximately 2000 genes were apparently changed their expression. Further proteomics analysis using 2-DE/MS confirmed the dramatic changes and provided additional information. We were aware that these changes are quite similar to the changes observed in epithelial-mesenchymal transition (EMT), most drastic changes in development and cancer metastasis. We thus further analyzed these changes using specific antibodies, and found distinct difference between these two phenomena. Among the differences, nuclear translocation of catenin beta 1 (CTNNB1) was inhibited by PCDH24-expression, subsequently some of the downstream nodes were suppressed. Although contact inhibition and cancer metastasis are completely opposite aspect of the cells, we expect that the identified differences will be key nodes to understand the relationship. We also expect that the nodes will be a target to modulate tumors arising stem cell transplantation (SCT), as well as a therapeutic target for cancer metastasis.
PCDH24-induced contact inhibition involves downregulation of beta-catenin signaling.
No sample metadata fields
View SamplesBRUCE was identified as a novel positive regulator of autophagy. By analyzing changes in mRNA levels, we wanted to determine whether BRUCE regulates autopahgy on a trancscriptional level. Overall design: Examination of changes in total mRNA levels comparing control (shRenilla) and BRUCE knockdown (shBruce) cells in full medium (FM) and starvation medium (Starv)
The IAP family member BRUCE regulates autophagosome-lysosome fusion.
Specimen part, Subject
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