Genomic and physiological analyses of the zebrafish atrioventricular canal reveal molecular building blocks of the secondary pacemaker region
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PROVIDER: PRJNA671857 | ENA |
REPOSITORIES: ENA
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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:To investigate how stage-specific activation of canonical Wnt signaling can induce the differentiation of atrioventricular canal cardiomyocytes，We employed single-cell RNA sequencing and ChIP-seq for H3K27ac to interrogate hPSC-derived cardiac cells.
2024-02-15 | GSE238107 | GEO
Project description: Not available
| S-EPMC8558220 | biostudies-literature
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. In this data set, we include expression data from atrioventricular canal (AVC) regions from Scx null and wild-type littermate controls at embryonic day 15.5. A total of 6 samples were analyzed; 3 valve regions from E15.5 Scx-/- mice, and 3 from E15.5 Scx+/+ wild-type littermate controls. Differential expression read counts are ranked based on p-value (<0.05).
2014-05-14 | E-GEOD-57423 | biostudies-arrayexpress
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
Project description:The molecular mechanisms governing heart development provide an important framework to understand congenital heart disease. The embryonic vertebrate heart tube develops an atrioventricular canal that divides the atrial and ventricular chambers, forms atrioventricular conduction tissue and organizes valve development. To better understand the molecular mechanism underlying atrioventricular canal versus chamber myocardium expression, a double-reporter transgenic mouse line was generated in which the expression of EGFP (green fluorescent protein) and Katushka (red fluorescent protein) are selectively expressed in the atrioventricular canal and in the chamber myocardium, respectively. We assessed the genome-wide H3K27ac pattern in isolated embryonic AV canal and in chamber cardiomyocytes, respectively.
2014-03-06 | GSE55611 | GEO
Project description:The molecular mechanisms governing heart development provide an important framework to understand congenital heart disease. The embryonic vertebrate heart tube develops an atrioventricular canal that divides the atrial and ventricular chambers, forms atrioventricular conduction tissue and organizes valve development. To better understand the molecular mechanism underlying atrioventricular canal versus chamber myocardium expression, a double-reporter transgenic mouse line was generated in which the expression of EGFP (green fluorescent protein) and Katushka (red fluorescent protein) are selectively expressed in the atrioventricular canal and in the chamber myocardium, respectively. We assessed the genome-wide H3K27ac pattern in isolated embryonic AV canal and in chamber cardiomyocytes, respectively. EGFP and Katushka-positive cells were purified by FACS and fixed. ChIP was performed with the truemicro ChIP (Diagenode) according to the manufacturer’s protocol using the H3K27ac antibody (abcam ab4729). Chipped DNA were subjected to library preparation using the 5500 Series SOLiD™ Systems ample preparation kit (Applied Biosystems) according to manufactures recommendations and sequenced using the 5500 wildfire system (SOLiD).
2014-03-06 | E-GEOD-55611 | biostudies-arrayexpress
Project description:Transcription generates local topological and mechanical constraints along the DNA fiber, driving for instance the generation of supercoiled chromosomal domains in bacteria. However, the global impact of transcription-based regulation of chromosome organization remains elusive. Notably, the scale of genes and operons in bacteria remains well below the resolution of chromosomal contact maps generated using Hi-C (~ 5 - 10 kb), preventing to resolve the impact of transcription on genomic organization at the fine-scale. Here, we combined sub-kb Hi-C contact maps and chromosome engineering to visualize individual transcriptional units (TUs) while turning off transcription across the rest of the genome. We show that each TU forms a discrete, transcription-induced 3D domain (TIDs). These local structures impose mechanical and topological constraints on their neighboring sequences at larger scales, bringing them closer together and restricting their dynamics. These results show that the primary building blocks of bacteria chromosome folding consists of transcriptional domains that together shape the global genome structure.
2023-12-01 | GSE213028 | GEO
Project description:Goals of this study were to identify new candidates involved in the development of the Atrioventricular cushions in the mouse heart. Keywords = Heart development Keywords = Atrioventricular cushions Keywords = Atrioventricular junction Keywords = Atrioventricular myocardium Keywords = embryonic day ED10.5-11.0 Keywords = ventricles Keywords: development analysis
2007-09-12 | GSE4903 | GEO