Effects of Trbp deletion on gene expession in mice hearts
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
SUBMITTER: Da-Zhi Wang
PROVIDER: E-GEOD-67658 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
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Project description:We generated the cardiac-specific knockout of Trbp (Trbp-cKO) in mice. We profiled the transcriptome in both wild-type and Trbp-cKO hearts, and found numerous genes were deregulated by deletion of Trbp. We also profiled miRNA expression both wild-type and Trbp-cKO hearts, and found expression of a subset of miRNA species was altered in Trbp-cKO hearts.
2015-04-27 | GSE67658 | GEO
Project description:In this project we explore the role of the master hypoxia regulator, Hypoxia inducible factor-1alpha (Hif-1a), in governing cardiac fibroblast (CF) function in homeostasis and following an acute ischaemic injury - myocardial infarction (MI). CF-specific Hif-1a conditional knockout (cKO) mice were generated by breeding Pdgfra-merCremer (PdgfraMCM/+) Cre recombinase driver mice with Hif-1a-floxed mice (Hif-1aflox/). In Hif-1afl/-; PdgfraMCM/+ progeny, Hif-1a could be conditionally deleted in adult CFs by tamoxifen (tam) administration. We also introduced a Cre-dependent R26tdTomato reporter allele allowing marking of Pdgfra+ CFs and their progeny. In this experiment, we first performed single-cell RNA sequencing (scRNA-seq) on tdTomato+ cells from the hearts of healthy cKO or heterozygous (HET) adult, male mice using the 10x Genomics Chromium system. We also performed scRNA-seq on tdTomato+/CD31-/CD45- cells from the hearts of cKO or HET mice at day-3 post-sham or -MI surgery.
2021-11-11 | E-MTAB-9583 | biostudies-arrayexpress
Project description:Heart valve formation initiates when endothelial cells of the heart transform into mesenchyme and populate the cardiac cushions. The transcription factor, SOX9, is highly expressed in the cardiac cushion mesenchyme, and is essential for heart valve development. Loss of Sox9 in mouse cardiac cushion mesenchyme alters cell proliferation, embryonic survival, and disrupts valve formation. Despite this important role, little is known regarding how SOX9 regulates heart valve formation or its transcriptional targets. Therefore, we mapped putative SOX9 binding sites by ChIP-Seq in embryonic day (E) 12.5 heart valves, a stage at which the valve mesenchyme is actively proliferating and initiating differentiation. Embryonic heart valves have been shown to express a high number of genes that are associated with chondrogenesis, including several extracellular matrix proteins and transcription factors that regulate chondrogenesis. Consequently, we compared regions of putative SOX9 DNA-binding between E12.5 heart valves and E12.5 limb buds. We identified context-dependent and contextâindependent SOX9 interacting regions throughout the genome. Analysis of context-independent SOX9 binding suggests an extensive role for SOX9 across tissues in regulating proliferation-associated genes including key components of the AP-1 complex. Integrative analysis of tissue-specific SOX9 interacting regions and gene expression profiles on Sox9-deficient heart valves demonstrated that SOX9 controls the expression of several transcription factors with previously identified roles in heart valve development, including Twist1, Sox4, Mecom/Evi1 and Pitx2. Together, our data identifies SOX9 coordinated transcriptional hierarchies that control cell proliferation and differentiation during valve formation. Examination of SOX9 binding sites in E12.5 atrioventricular canal (AVC) and E12.5 embryonic limb and mRNA expression profiling in E12.5 WT and Sox9 mutant AVCs, in duplicate.
2015-11-05 | E-GEOD-73225 | biostudies-arrayexpress
Project description:To determine differential gene expression in Ctnnb1 CKO mice testis compared to CTRL mice testis. The Agilent Mouse Whole Genome 4x44K array (Samples are from pooled total testes RNA from 4 CTRL and 4 Ctnnb1 CKO mice; dye-swap was performed.)
2012-03-20 | E-GEOD-30773 | biostudies-arrayexpress
Project description:Purpose: Next-generation sequencing (NGS) provides the change of cellular pathways at the transcriptomic level. The overall goal for this research are to compare the transcriptome profiling by NGS in cardiomyocyte-specific FAM210A conditional knockout (cKO) hearts and control (Ctrl) hearts at two different time points and to evaluate the signaling pathways affected by FAM210A deficiency in the heart at the molecular level. Methods: Cardiac mRNA profiles of FAM210A cKO and Ctrl hearts were generated by deep sequencing in triplicate at the late stage (~10 weeks post Fam210a cKO by tamoxifen induction) and in quadruplicates at the early stage (~5 weeks post Fam210a cKO by tamoxifen induction). Results: Using an optimized data analysis workflow from the Genomic Research Center at the University of Rochester, we mapped ~30 millian sequence reads per sample to the mouse genome in the hearts of Ctrl and Fam210a cKO mice at both early and late stages. RNA-seq data comfirmed the knockout of FAM210A in the Fam210a cKO hearts. We identified differentially expressed genes at both early and late stages of FAM210A cKO heart compared with Ctrl hearts (adjust P valuse <0.05). Among upregulated genes, we observed enhanced integrated stress response (ISR) gene signature at both early and late stages in Fam210a cKO hearts compared with Ctrl hearts, including aminoacyl-tRNA synthetases, amino acid synthases, and one-carbon metabolic enzymes. The downregulated genes were not common between the two stages. At the early stage, the top enriched pathways include negative regulation of blood coagulation and wound healing and fatty acid metabolic process. In contrast, at the late stage, the major pathways include sulfide oxidation, glucose import, and mitochondrial ETC complex assembly. Conclusions: Our study provides the first detailed transcriptomic anslysis of cardiomyocyte specific knockout of Fam210a in the heart at two different time-points by NGS. The RNA-seq data reported here provide a framework for comparative investigation of expression profiles in the hearts of FAM210A cKO compared with Ctrl hearts. Based on our analysis, we conclude that ISR is persistently activated in Fam210a cKO hearts, which may be a pro-survival compensatory response caused by the dysfunction of mitochondria in Fam210a cKO hearts. ISR activation can reprogram global cap-dependent translation and cellular metabolism simultaneously.
2023-02-01 | GSE195957 | GEO
Project description:Mice knocked-out or wild type for the NAPE PLD gene specifically in adipose tissue, were recruited for this expression profiling experiment. Each group of mice (WT versus cKO) were fed with a control diet or a high fat diet. Then mice were sacrificed and adipose tissue samples form the subcutaneous adipose tissue were processed for RNA extraction. Total RNA of each sample was then pooled with those of the same group and treatment for microarray hybridization. two groups of mice: (I) NAPE PLD WT and NAPE PLD KO. Each group was submitted to a diet treatment: (I) control diet and (II) high fat diet.
2015-03-06 | E-GEOD-56852 | biostudies-arrayexpress
Project description:PGM1 deficiency is recognized as the third most common N-linked Congenital Disorders of Glycosylation (CDG) in humans. Affected individuals present with liver, musculoskeletal, endocrine, and coagulation symptoms; however, the most life-threatening complication is an early onset of dilated cardiomyopathy (DCM). Recently, we discovered that oral D-galactose supplementation improved liver disease, endocrine and coagulation abnormalities, but does not alleviate the fatal cardiomyopathy and the associated myopathy. To study the pathobiology of the cardiac disease observed in PGM1-CDG, we constructed a novel cardiomyocyte-specific conditional Pgm2 (mouse ortholog of human PGM1) knockout (Pgm2 cKO) mouse model. Echocardiography studies corroborated a DCM phenotype with significantly reduced ejection fraction and left ventricular dilatation similar to those seen in individuals with PGM1-CDG. Histological studies demonstrated excess glycogen accumulation and fibrosis, while ultrastructural analysis revealed Z-disk disarray and swollen/fragmented mitochondria. We observed similar ultrastructural pathology in the cardiac explant of an individual with PGM1-CDG. We found decreased mitochondrial function in the heart of Pgm2 cKO mice. Transcriptomic analysis of hearts from Pgm2 cKO mice demonstrated a gene signature of DCM. Although proteomics revealed only mild changes in global protein expression in left ventricular tissue of Pgm2 cKO mice, a glycoproteomic analysis revealed an overall decreased protein glycosylation with significant glycosylation defects in sarcolemmal proteins including different subunits of laminin protein. Finally, augmentation of PGM1 in KO mice via AAV9-PGM1 gene replacement therapy prevented and halted the progression of the DCM phenotype.
2023-08-18 | PXD036271 | Pride
Project description:We used Illumina Small RNA and RNA-Seq kits to prepare both small RNA and RNA-Seq libraries from total RNA isolated from either leptotenze/zygotene or pachytene spermatocytes purified from either Dgcr8 or Dicer germline conditional knockout mice. Conditional knockout mice were generated by using a Ddx4 promoter to drive cre excision of either Dgcr8 or Dicer at embryonic day 18. Mixed leptotene/zygotene or pachytene spermatocytes were then isolated from the testis of adult conditional knockout mice, along with paired WT littermates as a control. RNA was isolated from these spermatocytes using Trizol. Small RNA or RNA-Seq libraries were then prepped using Illumina's sequencing library preparation kits.
2015-05-06 | E-GEOD-63166 | biostudies-arrayexpress
Project description:TRBP has two known functions as Dicer co-factor and PKR inhibitor. However, the role of TRBP in miRNA biogenesis is controversial and its regulation of PKR in mitosis remains unexplored. Here, we generate TRBP KO HeLa cells and find that TRBP depletion alters Dicer processing sites of a subset of miRNAs, but does not affect Dicer stability, miRNA abundance, or Argonaute loading. By generating PACT, another Dicer interactor, and TRBP/PACT double-KO cells, we further show that TRBP and PACT do not functionally compensate each other and that only TRBP contributes to Dicer processing. We also report that TRBP is hyperphosphorylated by JNK in M phase when PKR is activated by cellular dsRNAs. Hyperphosphorylation potentiates the inhibitory activity of TRBP on PKR, suppressing PKR in M-G1 transition. By generating the first human TRBP KO, our study clarifies the role of TRBP and unveils negative feedback regulation of PKR through TRBP phosphorylation.
2014-09-16 | GSE61458 | GEO
Project description:Effects of Trbp deletion on gene expession in mice hearts
| PRJNA280580 | ENA