Expression data from embryonic day 15.5 atrioventricular canal regions were isolated from Scx-/- and Scx+/+ mice.
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
SUBMITTER: Damien Barnette
PROVIDER: E-GEOD-57423 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
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Project description:Purpose: Our lab has previously shown that Scleraxis (Scx) is require for proper valve development in vivo. In order to fully explore gene networks regulated by Scx during the vital stages of valve remodeling , high throughput RNA-squencing was performed. Results:There were a total of 18,810 genes were detected. A total of 864 genes were differentially expressed Scx null AVC regions: 645 being upregulated and 217 downregulated.
2014-05-14 | GSE57423 | GEO
Project description:Malformations of the cardiovascular system are the most common type of birth defect in humans, affecting predominantly the formation of valves and septa. During heart valve and septa formation, cells from the atrio-ventricular canal (AVC) and outflow tract (OFT) regions of the heart undergo an epithelial-to-mesenchymal transformation (EMT) and invade the underlying extracellular matrix to give rise to endocardial cushions. Subsequent maturation of newly formed mesenchyme cells leads to thin stress-resistant leaflets. TWIST1 is a basic helix-loop-helix transcription factor expressed in newly formed mesenchyme cells of the AVC and OFT that has been shown to play roles in cell survival, cell proliferation and differentiation. However, the role and downstream targets of TWIST1 during heart valve formation remain unclear. To identify genes important for heart valve development downstream of Twist1 we performed global gene expression profiling of AVC, OFT, atria and ventricles of the embryonic day 10.5 mouse heart by tag-sequencing (Tag-seq). Using this resource we identified a novel set of 1246 genes, including 201 regulators of transcription, enriched in the valve forming regions of the heart. We compared these genes to a Tag-seq library from the Twist1 null developing valves revealing significant gene expression changes. These changes were consistent with a role of TWIST1 in controlling differentiation of mesenchymal cells following their transformation from endothelium in the mouse. To study the role of TWIST1 at the DNA level we performed chromatin immunoprecipitation and identified novel direct targets of TWIST1 in the developing heart valves. Our findings are consistent with a role for TWIST1 in the differentiation of AVC mesenchyme post-EMT in the mouse, and suggest that TWIST1 exerts its function by direct DNA binding to activate valve specific gene expression. Profiled the AVC, OFT, atria and ventricles of the embryonic day 10.5 mouse heart by tag-sequencing (Tag-seq) (no replicates). We also produced a Tag-seq library from Twist1 null developing valves to reveal the gene expression changes associated with loss of this gene.
2012-06-01 | E-GEOD-37746 | biostudies-arrayexpress
Project description:The atrioventricular canal (AVC) is the site where key structures responsible for functional division between heart regions are established, most importantly, the atrioventricular (AV) conduction system and cardiac valves. To elucidate the mechanism underlying AVC development and function, we utilized transgenic zebrafish line sqet31Et expressing EGFP in the AVC to isolate this cell population and profile its transcriptome at 48 and 72 hpf. The zebrafish AVC transcriptome exhibits hallmarks of mammalian AV node, including the expression of genes implicated in its development and those encoding connexins forming low conductance gap junctions. Transcriptome analysis uncovered protein-coding and noncoding transcripts enriched in AVC, which have not been previously associated with this structure, as well as dynamic expression of epithelial-to-mesenchymal transition markers and components of TGF-β, Notch, and Wnt signaling pathways likely reflecting ongoing AVC and valve development. Using transgenic line Tg(myl7:mermaid) encoding voltage-sensitive fluorescent protein, we show that abolishing the pacemaker-containing sinoatrial ring (SAR) through Isl1 loss of function resulted in spontaneous activation in the AVC region, suggesting that it possesses inherent automaticity although insufficient to replace the SAR. The SAR and AVC transcriptomes express partially overlapping species of ion channels and gap junction proteins, reflecting their distinct roles. Besides identifying conserved aspects between zebrafish and mammalian conduction systems, our results established molecular hallmarks of the developing AVC which underlies its role in structural and electrophysiological separation between heart chambers. This data constitutes a valuable resource for studying AVC development and function, and identification of novel candidate genes implicated in these processes.
2021-09-24 | GSE160107 | GEO
Project description:Malformations of the cardiovascular system are the most common type of birth defect in humans, affecting predominantly the formation of valves and septa. During heart valve and septa formation, cells from the atrio-ventricular canal (AVC) and outflow tract (OFT) regions of the heart undergo an epithelial-to-mesenchymal transformation (EMT) and invade the underlying extracellular matrix to give rise to endocardial cushions. Subsequent maturation of newly formed mesenchyme cells leads to thin stress-resistant leaflets. TWIST1 is a basic helix-loop-helix transcription factor expressed in newly formed mesenchyme cells of the AVC and OFT that has been shown to play roles in cell survival, cell proliferation and differentiation. However, the role and downstream targets of TWIST1 during heart valve formation remain unclear. To identify genes important for heart valve development downstream of Twist1 we performed global gene expression profiling of AVC, OFT, atria and ventricles of the embryonic day 10.5 mouse heart by tag-sequencing (Tag-seq). Using this resource we identified a novel set of 1246 genes, including 201 regulators of transcription, enriched in the valve forming regions of the heart. We compared these genes to a Tag-seq library from the Twist1 null developing valves revealing significant gene expression changes. These changes were consistent with a role of TWIST1 in controlling differentiation of mesenchymal cells following their transformation from endothelium in the mouse. To study the role of TWIST1 at the DNA level we performed chromatin immunoprecipitation and identified novel direct targets of TWIST1 in the developing heart valves. Our findings are consistent with a role for TWIST1 in the differentiation of AVC mesenchyme post-EMT in the mouse, and suggest that TWIST1 exerts its function by direct DNA binding to activate valve specific gene expression.
2012-06-01 | GSE37746 | GEO
Project description:One third of cardiac congenital diseases affect cardiac valves. Genetically modifiedmice have advancedourunderstandingof valve development and related pathologies. However, little is known with regard tohuman valve development.We aimed to derive a novel human pluripotent stem cellmodel in order to decode the early steps of human valvulogenesis.Human MesP1+mesodermal cells were differentiated toward the fate of second heart field progenitors and then to a selected population of pre-valvular endocardial cells. Gene arrays revealed that these human prevalvular cells (HPVC) express patterns of genes similar to those expressed in theatrioventricular canal (AVC) endocardium of E9.0 mouse embryos. In mice this developmental time precedes endocardial mesenchymal transition (EndoMT),which is required for mature valve formation.HPVC treated with BMP2, cultured onto chick or mouse AVC cushions, or transplanted into the outflow tract or AVC of embryonic chick and mouse hearts, underwent EndoMTin both a Notch-dependent and independent-manner and expressed markers of valve mesenchymal cells and fibroblasts.Similar to the previously described valve interstitial cells (VICs), HPVC also differentiate into tendinous/chondrogenic cells. Our study indicates thathuman pluripotent stem cells canrecapitulate early valvulogenesis and thus provide a powerful model to further decipher the origin and lineage contributionof different valvular cell typesin humans.
2019-01-23 | GSE73619 | GEO
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:One third of cardiac congenital diseases affect cardiac valves. Genetically modified mice have advanced our understanding of valve development and related pathologies. However, little is known with regard to human valve development.We aimed to derive a novel human pluripotent stem cell model in order to decode the early steps of human valvulogenesis. Human MesP1+mesodermal cells were differentiated toward the fate of second heart field progenitors and then to a selected population of pre-valvular endocardial cells. Gene arrays revealed that these human prevalvular cells (HPVC) express patterns of genes similar to those expressed in the atrioventricular canal (AVC) endocardium of E9.0 mouse embryos. In mice this developmental time precedes endocardial mesenchymal transition (EndoMT),which is required for mature valve formation. HPVC treated with BMP2, cultured onto chick or mouse AVC cushions, or transplanted into the outflow tract or AVC of embryonic chick and mouse hearts, underwent EndoMTin both a Notch-dependent and independent-manner and expressed markers of valve mesenchymal cells and fibroblasts. Similar to the previously described valve interstitial cells (VICs), HPVC also differentiate into tendinous/chondrogenic cells. Our study indicates tha thuman pluripotent stem cells canrecapitulate early valvulogenesis and thus provide a powerful model to further decipher the origin and lineage contribution of different valvular cell types in humans.
2019-01-22 | GSE73546 | GEO
Project description:Defective valve and septa formation constitute a substantial part of congenital heart defects affecting the neonate or the adult. During cardiac development, restricted myocardial Bmp2 expression is a key signal for the specification and patterning of the valve-forming field in the atrio-ventricular canal (AVC) region and the initiation of the epithelial-mesenchyme transition (EMT) that gives rise to the valve primordia. We have generated a mouse transgenic line conditionally expressing Bmp2. Nkx2.5Cre-driven Bmp2 overexpression in the myocardium leads to foetal lethality, due to valve and chamber dysmorphogenesis, and rescue of the AVC specification defect of Bmp2-null embryos. Nkx2.5Cre/+;Bmp2tg/+ transgenic embryos show ventricular septal defect, thickened valves, enlarged trabeculae and dilated ventricles, whose endocardium is able to undergo EMT when explanted onto collagen gels. Gene profile and marker analysis indicates that cellular proliferation is increased and chamber differentiation and patterning is impaired in Nkx2.5Cre/+;Bmp2tg/+ embryos, but the ventricular-specific gene expression program is not abolished. We obtained similar results using a second myocardial driver (cTnTCre) to activate Bmp2 expression, but not with an endothelial-specific one (Tie2Cre), as Tie2Cre/+;Bmp2tg/+ mice are normal and survive to adulthood, indicating that Bmp2 must emanate from the myocardium to exert its EMT-driving and cardiomyocyte maturation blocking effect. Forced Bmp2 expression in vitro stimulates EBs proliferation and blocks their progression into cardiomyogenesis, an effect partially rescued by Noggin. These data show that widespread myocardial Bmp2 expression directs ectopic valve primordium formation and maintains chamber myocardium and early cardiac progenitors in a primitive, proliferative state, identifying Bmp2 as a potential factor for the expansion of immature cardiomyocytes.
2018-04-11 | GSE100810 | GEO
Project description:Rationale: A critical step in heart development is the coordinated formation of nodal myocardium and cushion tissue from the atrioventricular canal (AVC). After its specification, the myocardium of the AVC aligns the chambers, forms the AV node, and induces the formation of the mesenchymal AV cushions, primordia of valves and septa, while it resists working myocardial differentiation. Objective: To assess what roles Tbx2 and Tbx3, two closely related T-box transcription factors expressed in the AVC, play in these processes. Methods and Results: We analyzed mice ectopically expressing Tbx3 in the atrial myocardium by genome-wide microarray and expression analysis. We found a prominent role for Tbx3 in defining the nodal phenotype by repressing working myocardial genes (sarcomeric, mitochondrial, fast conduction) and cell proliferation regulators, and in inducing node-associated genes. Moreover, there was a striking induction of genes associated with endocardial cushions and mesenchyme. Using gain-of-function models, we found that in the developing heart both Tbx2 and Tbx3 induce ectopic Bmp2 and Tgfb2 expression and endocardial cushion formation. Analysis of compound Tbx2/Tbx3 mutant embryos revealed that upon loss of more than two functional alleles, expansion of the AV myocardium does not occur and AV cushions fail to form. Conclusions: Tbx2 and Tbx3 locally stimulate development of the AVC myocardium, induce the AV nodal phenotype therein and trigger AV cushion formation from the overlying AV endocardium, providing a mechanism for the colocalization and coordination of these two important processes in heart development.
2014-08-01 | GSE10318 | GEO
Project description:Rationale: A critical step in heart development is the coordinated formation of nodal myocardium and cushion tissue from the atrioventricular canal (AVC). After its specification, the myocardium of the AVC aligns the chambers, forms the AV node, and induces the formation of the mesenchymal AV cushions, primordia of valves and septa, while it resists working myocardial differentiation. Objective: To assess what roles Tbx2 and Tbx3, two closely related T-box transcription factors expressed in the AVC, play in these processes. Methods and Results: We analyzed mice ectopically expressing Tbx3 in the atrial myocardium by genome-wide microarray and expression analysis. We found a prominent role for Tbx3 in defining the nodal phenotype by repressing working myocardial genes (sarcomeric, mitochondrial, fast conduction) and cell proliferation regulators, and in inducing node-associated genes. Moreover, there was a striking induction of genes associated with endocardial cushions and mesenchyme. Using gain-of-function models, we found that in the developing heart both Tbx2 and Tbx3 induce ectopic Bmp2 and Tgfb2 expression and endocardial cushion formation. Analysis of compound Tbx2/Tbx3 mutant embryos revealed that upon loss of more than two functional alleles, expansion of the AV myocardium does not occur and AV cushions fail to form. Conclusions: Tbx2 and Tbx3 locally stimulate development of the AVC myocardium, induce the AV nodal phenotype therein and trigger AV cushion formation from the overlying AV endocardium, providing a mechanism for the colocalization and coordination of these two important processes in heart development. Nppa-Cre4 (Cre4) mice were crossed with CT mice to obtain efficient activation of Tbx3 in atria of double transgenic Cre4-CT mice, as previously described (Hoogaars et al., 2007). To investigate the gene expression profile of atria of Cre4-CT mice, we performed whole genome microarray analysis using Sentrix Mouse-6 oligonucleotide beadchips. We compared the atrial gene expression profiles of six male double transgenic Cre4-CT mice and six male Cre4 control mice.
2014-08-01 | E-GEOD-10318 | biostudies-arrayexpress