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 SamplesGlobal gene expression profiling of human iPSC and the iPSC-derived presomitic mesoderm(PSM), somite(SM), and the derivatives, dermomyotome(DM), dermatome(D), myotome(MYO), sclerotome(SCL) and syndetome(SYN).
Modeling human somite development and fibrodysplasia ossificans progressiva with induced pluripotent stem cells.
Specimen part, Time
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 SamplesAnalyzed differentially expressed genes among FOP- or resFOP-iMSCs treated by several ligands:
Neofunction of ACVR1 in fibrodysplasia ossificans progressiva.
Specimen part
View SamplesGlobal gene expression profiling of FOP-iMSCs after chondrogenic differentiation with ERBB2 inhibitors
An mTOR Signaling Modulator Suppressed Heterotopic Ossification of Fibrodysplasia Ossificans Progressiva.
Specimen part, Treatment
View SamplesComparison of gene expressions among FOP- or resFOP-iMSCs after chondrogenic differentiation with or without Activin-A.
Neofunction of ACVR1 in fibrodysplasia ossificans progressiva.
Specimen part
View SamplesComparison of gene expressions among FOP- or resFOP-iMSCs after chondrogenic differentiation with Activin-A, BMP-7 or TGF-B3
Activin-A enhances mTOR signaling to promote aberrant chondrogenesis in fibrodysplasia ossificans progressiva.
Specimen part
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 SamplesWe analyzed the effects of cellular context on the function of the synovial sarcoma-specific fusion protein, SS18-SSX, using human pluripotent stem cells containing the drug-inducible SS18-SSX gene. To investigate the cell-type-dependent effecfts of SS18-SSX, we performed gene expression profiling experiments.
SS18-SSX, the Oncogenic Fusion Protein in Synovial Sarcoma, Is a Cellular Context-Dependent Epigenetic Modifier.
Specimen part
View Samples