Growth and expansion of ventricular chambers is essential during cardiogenesis and is achieved by proliferation of cardiac progenitors that are not fully differentiated. Disruption of this process can lead to prenatal lethality. In contrast, adult cardiomyocytes achieve growth through hypertrophy rather than hyperplasia. Although epicardial-derived signals may contribute to the proliferative process in myocytes, the factors and cell types responsible for development of the ventricular myocardial thickness are unclear. Moreover, the function of embryonic cardiac fibroblasts, derived from epicardium, and their secreted factors are largely unknown. Using a novel co-culture system, we found that embryonic cardiac fibroblasts induced proliferation of cardiomyocytes, in contrast to adult cardiac fibroblasts that promoted myocyte hypertrophy. We identified fibronectin, collagen and heparin-binding EGF-like growth factor as embryonic cardiac fibroblast-specific signals that collaboratively promoted cardiomyocyte proliferation in a paracrine fashion. b1 integrin was required for this proliferative response, and ventricular cardiomyocyte-specific deletion of b1 integrin in mice resulted in reduced myocardial proliferation and impaired ventricular compaction. These findings reveal a previously unrecognized paracrine function of embryonic cardiac fibroblasts in regulating cardiomyocyte proliferation.
Cardiac fibroblasts regulate myocardial proliferation through beta1 integrin signaling.
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View SamplesGrowth and expansion of ventricular chambers is essential during cardiogenesis and is achieved by proliferation of cardiac progenitors that are not fully differentiated. Disruption of this process can lead to prenatal lethality. In contrast, adult cardiomyocytes achieve growth through hypertrophy rather than hyperplasia. Although epicardial-derived signals may contribute to the proliferative process in myocytes, the factors and cell types responsible for development of the ventricular myocardial thickness are unclear. Moreover, the function of embryonic cardiac fibroblasts, derived from epicardium, and their secreted factors are largely unknown. Using a novel co-culture system, we found that embryonic cardiac fibroblasts induced proliferation of cardiomyocytes, in contrast to adult cardiac fibroblasts that promoted myocyte hypertrophy. We identified fibronectin, collagen and heparin-binding EGF-like growth factor as embryonic cardiac fibroblast-specific signals that collaboratively promoted cardiomyocyte proliferation in a paracrine fashion. b1 integrin was required for this proliferative response, and ventricular cardiomyocyte-specific deletion of b1 integrin in mice resulted in reduced myocardial proliferation and impaired ventricular compaction. These findings reveal a previously unrecognized paracrine function of embryonic cardiac fibroblasts in regulating cardiomyocyte proliferation.
Cardiac fibroblasts regulate myocardial proliferation through beta1 integrin signaling.
No sample metadata fields
View SamplesGrowth and expansion of ventricular chambers is essential during cardiogenesis and is achieved by proliferation of cardiac progenitors that are not fully differentiated. Disruption of this process can lead to prenatal lethality. In contrast, adult cardiomyocytes achieve growth through hypertrophy rather than hyperplasia. Although epicardial-derived signals may contribute to the proliferative process in myocytes, the factors and cell types responsible for development of the ventricular myocardial thickness are unclear. Moreover, the function of embryonic cardiac fibroblasts, derived from epicardium, and their secreted factors are largely unknown. Using a novel co-culture system, we found that embryonic cardiac fibroblasts induced proliferation of cardiomyocytes, in contrast to adult cardiac fibroblasts that promoted myocyte hypertrophy. We identified fibronectin, collagen and heparin-binding EGF-like growth factor as embryonic cardiac fibroblast-specific signals that collaboratively promoted cardiomyocyte proliferation in a paracrine fashion. b1 integrin was required for this proliferative response, and ventricular cardiomyocyte-specific deletion of b1 integrin in mice resulted in reduced myocardial proliferation and impaired ventricular compaction. These findings reveal a previously unrecognized paracrine function of embryonic cardiac fibroblasts in regulating cardiomyocyte proliferation.
Cardiac fibroblasts regulate myocardial proliferation through beta1 integrin signaling.
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View Samplesmicroarray was done on Heart tissue from ko and wt
Dysregulation of cardiogenesis, cardiac conduction, and cell cycle in mice lacking miRNA-1-2.
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View SamplesThe Arabidopsis thaliana defense regulator EDM2 was previously shown to be specifically required for disease resistance to the pathogenic oomycete Hyaloperonospora parasitica aradidopsis mediated by the R protein RPP7. We found EDM2 to have a promoting effect on several distinct developmental processes, such as leaf pavement cell development, vegetative phase change or the floral transition. We further identified the atypical protein kinase WNK8 to physically interact with EDM2 in nuclei.
Co-option of EDM2 to distinct regulatory modules in Arabidopsis thaliana development.
Specimen part
View SamplesThe molecular mechanism by which lncRNAs derived from the promoter region where the transcriptional machinery is assembled regulate the expression of neighboring genes during cell differentiation is largely unknown. Myogenesis process has been studied as a model of cell differentiation. Using this model, we found a novel lncRNA, Myoparr, expressed from the promoter region of myogenin gene, one of the regulators of myogenesis. We show that Myoparr regulates the expression of myogenin in vitro and in vivo. In addition, we identified Ddx17 and hnRNPK as Myoparr-binding-proteins. We compared the Transcriptome profiles of C2C12 cells (mouse myoblast cell line) with or without siRNAs against myogenin, Myoparr, Ddx17, and hnRNPK during myogenesis.
Data describing the effects of depletion of <i>M</i><i>yoparr</i>, <i>myogenin</i>, <i>Ddx17</i>, and <i>hnRNPK</i> in differentiating C2C12 cells.
Specimen part, Cell line
View SamplesACC Synthase (ACS) is the key regulatory enzyme in the ethylene biosynthesis in plants. It catalyzes the conversion of s-adenosylmethionine (SAM) to 1-aminocyclopropane-1-carboxylic acid (ACC), the precursor of ethylene. Arabidopsis has nine ACS genes. The goal of the project is to inactivate each gene by insertional mutagenesis and amiRNA technology and eventually construct a null ACS mutant. We have been recently able to achieve this goal. Furthermore, we wanted to know how inactivation of individual ACS genes affects global gene expression.
A combinatorial interplay among the 1-aminocyclopropane-1-carboxylate isoforms regulates ethylene biosynthesis in Arabidopsis thaliana.
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View SamplesWe performed a global analysis of both miRNAs and mRNAs expression across sixteen human cell lines and extracted negatively correlated pairs of miRNA and mRNA which indicate miRNA-target relationship. The many of known-target of miR-124a showed negative correlation, suggesting our analysis were valid. We further extracted physically relevant miRNA-target gene pairs, applying computational target prediction algorism with inverse correlations of miRNA and mRNA expression. Furthermore, Gene Ontology-based annotation and functional enrichment analysis of the extracted miRNA-target gene pairs indicated putative functions of miRNAs.
Global correlation analysis for micro-RNA and mRNA expression profiles in human cell lines.
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View SamplesA promoter associated lncRNA Myoparr is involved in the regulation of skeletal muscle atrophy caused by denervation. However, the molecular mechanism by which Myoparr regulates the expression of downstream genes in skeletal muscle tissue is largely unknown. Thus, we compared the Transcriptome profiles of denervated tibialis anterior muscles transfected with control or Myoparr shRNA.
Long Non-Coding RNA <i>Myoparr</i> Regulates GDF5 Expression in Denervated Mouse Skeletal Muscle.
Sex, Specimen part, Cell line, Treatment
View SamplesMicroRNAs are small non-coding RNA species, some of which are playing important roles in cell differentiation. However, the level of participations of microRNAs in epithelial cell differentiation is largely unknown. Here, we found that expression levels of four microRNAs (miR-210, miR-338-3p, miR-33a and miR-451) were significantly increased in differentiated stage of T84 cells, compared with undifferentiated stage. Additionally, we demonstrate that miR-338-3p and miR-451 contribute to the formation of epithelial basolateral polarity by facilitating translocalization of beta1 integrin to the basolateral membrane. However, candidate target mRNAs of miR-338-3p and miR-451 and the mechanism behind observed phenomena is uncertain. Then, we performed comprehensive gene expression analysis to identify candidate target mRNAs and understand their mechanisms.
MicroRNA-338-3p and microRNA-451 contribute to the formation of basolateral polarity in epithelial cells.
Cell line, Treatment, Time
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