Similar Datasets
Project description:To characterize bag3 cardiomyopathy model in adult zebrafish through RNA-Seq
| PRJNA560203 | ENA
Project description:We sequenced mRNA from embryonic heart of zebrafish larvae 4 days post fertilization, adult heart of 6-month-old WIK fish, and adult muscle of adult fish consisting of both fast-twitch and slow-twitch fibers.
2017-05-01 | GSE85416 | GEO
Project description:Loss of Bcl2-associated anthanogene 3 (BAG3) is associated with dilated cardiomyopathy (DCM). Recent studies show that BAG3 regulates sarcomere protein turnover in cardiomyocytes (CMs). However, the function of BAG3 in other cell types of the heart is unknown. In this study, we used an isogenic pair of BAG3 knockout and wild-type human induced pluripotent stem cells (hiPSC) to interrogate the function of BAG3 in hiPSC-derived cardiac fibroblasts (CFs). Generating a series of conditional knockout (cKO) engineered heart tissues, we determined the contribution of CF BAG3 to engineered heart tissue function. Despite normal CM genotype, the loss of fibroblast-specific BAG3 (FBKO) caused a reduction in contractile force and an increase in cardiac fibrosis in the engineered heart tissues, recapitulating the phenotype of DCM. Using culture substrates with defined stiffness, we decoupled the mechanical activation of fibroblasts from their ligand response. In BAG3-/- CFs, we observed an increased sensitivity to transforming growth factor β (TGFβ) signaling and activation of a fibrogenic response when cultured at physiological stiffness (8kPa). Mechanistically, loss of BAG3 increased transforming growth factor receptor 2 (TGFBR2) levels. BAG3 binds TGFBR2 and mediates its ubiquitination and proteasomal degradation. To further validate these results, we performed single-nuclei sequencing of cardiac tissue from DCM patients carrying pathogenic BAG3 mutations. Mutations in BAG3 increased fibrotic gene expression in cardiac fibroblasts. Together, these results extend our understanding of the roles of BAG3 in heart disease beyond the cardiomyocyte-centric view. This study also highlights the ability of hiPSC-based models and tissue engineering to answer questions about the cell-type specific aspects of cardiac disease.
2024-09-16 | GSE261750 | GEO
Project description:Cardiac-specific Bag3-P209L transgenic (Tg+) mice develop dilated cardiomyopathy by 12 months of age. The goals of this project are to utilize RNA-sequencing to compare both cardiomyocyte and cardiac fibroblast transcriptomes between aged Bag3-P209L Tg+ and Bag3-WT mice to identify cardiomyocyte and fibroblast specific gene sets that contribute to the functional and morphological changes previously identified in Bag3-P209L Tg+ hearts.
2021-06-25 | GSE116200 | GEO
Project description:Mutations in the Hsp70 co-chaperone Bcl2-associated athanogene 3 (Bag3) result in myofibrillar myopathy and pediatric hypertrophic cardiomyopathy (pHCM) in human patients, but the pathological mechanisms underlying Bag3 dysfunction in the developing heart have remained unclear. Here we show that conditional ablation of Bag3 in cardiomyocytes (CMs) results in progressive cardiomyopathy accompanied by increased autophagic flux and autophagosome accumulation in the early post-natal period. Autophagy inhibition via acute administration of chloroquine (CQ) results in transient accumulation of cardiac proteins in the detergent-insoluble fraction, implying a role for autophagy in the degradation of unfolded proteins in the absence of Bag3 co-chaperone activity. Exacerbated autophagy in Bag3 deficient CMs leads to decreased soluble levels of proteins involved in cardiac contraction and conduction, including the gap junction protein connexin 43 (Cx43). Importantly, chronic CQ treatment during the early post-natal period results in a significant amelioration of the pathological phenotype, with recovered contractile performances and restoration of soluble levels of autophagy-targeted proteins. We therefore conclude that loss of Bag3 in CMs leads to autophagic flux exacerbation and that CQ treatment is relevant to therapeutic strategies for Bag3-dependent pHCM patients.
2024-06-05 | PXD016095 | Pride
Project description:Gene expression profiling of wild-type, BAG3-KO and BAG3-R477H iPSC-derived cardiomyocytes
2019-10-10 | GSE138633 | GEO
Project description:Copy number variants (CNVs) represent a substantial source of genomic variation in vertebrates, but the zebrafish reference genome has no annotated CNV information. We developed a zebrafish CNV map using 80 zebrafish genomes from laboratory strains (AB, Tubingen, and WIK) and one native population, identifying 6,080 CNV elements. Overlapping or adjacent CNVs account for 14.6% of the genome, representing four times the CNV levels from other vertebrates including humans. Highest intra-specific CNV levels were observed for Tubingen, a common laboratory strain due to high fecundity. Tubingen variation likely represents higher initial population size and composite population founders initiating the laboratory strain. Extensive zebrafish CNVs, along with associated phenotypic impacts, advocates for increased usage of isogenic strains for genetic studies intended for human disease translation. 7 full sib adult hybrid fish used for expression Quantatitive Trait Loci (eQLT) analysis to support CNV affects on gene expresion in zebrafish.
2011-12-27 | E-GEOD-28239 | biostudies-arrayexpress
Project description:Copy number variants (CNVs) represent a substantial source of genomic variation in vertebrates, but the zebrafish reference genome has no annotated CNV information. We developed a zebrafish CNV map using 80 zebrafish genomes from laboratory strains (AB, Tubingen, and WIK) and one native population, identifying 6,080 CNV elements. Overlapping or adjacent CNVs account for 14.6% of the genome, representing four times the CNV levels from other vertebrates including humans. Highest intra-specific CNV levels were observed for Tubingen, a common laboratory strain due to high fecundity. Tubingen variation likely represents higher initial population size and composite population founders initiating the laboratory strain. Extensive zebrafish CNVs, along with associated phenotypic impacts, advocates for increased usage of isogenic strains for genetic studies intended for human disease translation. 7 full sib adult hybrid fish used for expression Quantatitive Trait Loci (eQLT) analysis to support CNV affects on gene expresion in zebrafish.
2011-12-27 | E-GEOD-28276 | biostudies-arrayexpress
Project description:Strains of commonly used wildtype zebrafish (Danio rerio) have both shared and unique genomic features such as SNPs and copy number variants. Unfortunately, exact lab strains are often unreported in the literature and the replication of studies in zebrafish may be negatively impacted by this fact. These data were collected to assess hepatic mRNA expression patterns between three common zebrafish strains (AB, Tuebingen, and WIK) to establish baseline differences across strains and between sexes.Baseline mRNA expression was analyzed in six individuals pers strain (three males and three females) using Agilent 4x44K gene expression microarrays . These data highlight the complexity of variation that exists within zebrafish and underscore the value of this model system as a valid representation of normal variation present in other species, including humans.
2018-01-01 | GSE100583 | GEO