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Single cell transcriptional profiles of endothelial cells sorted from the hearts with ablation of Wnt/beta-catenin signaling activating cardiomyocytes and without ablation [scRNA-seq]

ABSTRACT: To understand how Wnt/β-catenin signaling-activated cardiomyocytes (β-cat ON CMs) promote coronary vessel development, we performed single-cell RNA sequencing of endothelial cells (ECs) sorted from the hearts ablated β-cat ON CMs and those from control hearts, respectively. Our analyses indicated that β-cat ON CMs regulates coronary vessel development by promoting arterialization, a step in the transition of endocardial ECs to coronary ECs.

ORGANISM(S): Danio rerio

PROVIDER: GSE223461 | GEO | 2024/08/23

REPOSITORIES: GEO

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Endocardial/endothelial angiocrines regulate cardiomyocyte development and maturation and induce features of ventricular non-compaction

Project description:Non-compaction cardiomyopathy is a devastating genetic disease caused by insufficient consolidation of ventricular wall muscle that can result in inadequate cardiac performance. Despite being the third most common cardiomyopathy, the mechanisms underlying the disease, including the cell types involved, are poorly understood. We have previously shown that endothelial cell-specific deletion of the chromatin remodeller gene Ino80 results in defective coronary vessel development that leads to ventricular non-compaction in embryonic mouse hearts. Here, we used single-cell RNA-sequencing to characterize endothelial and endocardial defects in Ino80-deficient hearts. We observed a pathological endocardial cell population in the non-compacted hearts and identified multiple dysregulated angiocrine factors that dramatically affected cardiomyocyte behaviour. We identified Col15A1 as a coronary vessel-secreted angiocrine factor, down-regulated by Ino80-deficiency, which functioned to promote cardiomyocyte proliferation. Furthermore, mutant endocardial and endothelial cells (ECs) AQ6 up-regulated expression of secreted factors, such as Tgfbi, Igfbp3, Isg15, and Adm, which decreased cardiomyocyte proliferation and increased maturation. These findings support a model where coronary ECs normally promote myocardial compaction through secreted factors, but that endocardial and ECs can secrete factors that contribute to non-compaction under pathological conditions.

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Transcriptional profiles of Wnt/beta-catenin signaling activated cardiomyocytes and the others in the atrioventricular canal of zebrafish heart [RNA-seq]

Project description:To understand the function of Wnt/β-catenin signaling-activated cardiomyocytes (β-cat ON CMs), we performed RNA-Seq on β-cat ON and OFF CMs at the atrioventricular canal (AVC) in the heart, respectively. Our analyses indicated that β-cat ON CMs upregulate genes related to blood vessel development.

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Single-cell transcriptional profiles of the atrioventricular canal of 1-month-old zebrafish treated with DMSO or IWR-1-endo

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Endocardium-to-coronary artery differentiation during heart development and regeneration involves sequential roles of Bmp2 and Cxcl12/Cxcr4.

Project description:Endocardial cells lining the heart lumen are coronary vessel progenitors during embryogenesis. Re-igniting this developmental process in adults could regenerate blood vessels lost during cardiac injury, but this requires additional knowledge on molecular regulators. Here, we use mouse genetics and scRNAseq to identify novel regulators of endocardial angiogenesis and precisely assess the role of CXCL12/CXCR4 signaling. Time-specific lineage tracing demonstrated that endocardial cells differentiated in coronary endothelial cells primarily at mid-gestation. A new mouse line reporting CXCR4 activity—along with cell-specific gene deletions—revealed it was specifically required for artery morphogenesis rather than angiogenesis. Integrating scRNAseq data of endocardial-derived coronary vessels from mid- and late-gestation identified a Bmp2-expressing transitioning population specific to mid-gestation. Bmp2 stimulated endocardial angiogenesis in vitro and in injured neonatal mouse hearts. Our data shed light on how understanding the molecular mechanisms underlying endocardial angiogenesis can identify new potential therapeutic targets promoting revascularization of the injured heart.

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Transcriptional profiling of purified endocardial and coronary vascular endothelial cells, isolated from murine embryonic hearts, at two developmental stages

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Tie2 regulates endocardial sprouting and myocardial trabeculation

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Effect of endothelial depletion of Wt1 on gene expression during coronary plexus sprouting in the heart

Project description:Coronary blood vessel formation is a highly regulated process in which endothelial cells (ECs) play an essential role. During the last years, new pieces of evidence have demonstrated WT1 expression in coronary ECs. However, its role in coronary blood vessel formation was almost unknown. Here we generated an inducible endothelial-specific Wt1KO mouse model (Wt1KOΔEC). The analysis of these mutant mice has demonstrated that deletion of Wt1 in coronary ECs impairs coronary blood vessels and myocardium development. The transcriptomic analysis of coronary ECs from Wt1KOΔEC mice demonstrated that deletion of Wt1 has a great impact on the molecular signature of coronary ECs that correlate with defects in cell proliferation, migration, and differentiation. These results provide novel insights into the role of WT1 in heart development and demonstrate that WT1 in ECs is required for coronary blood vessel formation.

2023-02-22 | GSE205616 | GEO

Regional differences in left ventricular shear stress contribute to heterogenity of the endocardial transcriptome

Project description:The role of shear stress, the frictional force of blood flow, on the endothelium has been well documented. Differences in shear stress can have profound effects on endothelial and blood vessel biology. Endothelial cells (ECs), termed endocardial ECs, line the heart chambers and are exposed to complex shear stress patterns. While it has been demonstrated that shear stress is important for heart development, little has been shown on the role of shear stress on adult ECs. 4D-MRI studies demonstrate regional differences in blood residence time. We sought to determine the effect of regional differences in endocardial shear stress on the endocardial transcriptome using RNA sequencing (RNA-seq) on 3 different regions (apex, mid-ventricle, outflow tract) from 8 adult pigs, for a total of 24 RNA-seq assays.

2015-12-31 | E-MTAB-3669 | biostudies-arrayexpress

Gene expression analysis from bulk RNA isolated from embryonic mouse hearts at time points E13.5 and E14.5 with and without disruption of endothelial Ino80

2022-07-17 | GSE154757 | GEO

In vivo endothelial transcriptional profiles of porcine coronary and iliac arteries

Project description:Phenotypic heterogeneity among arterial ECs is particularly relevant to atherosclerosis since the disease occurs predominantly in major arteries, which vary in their atherosusceptibility. To explore EC heterogeneity, we used DNA microarrays to compare gene expression profiles of freshly harvested porcine coronary and iliac artery ECs. We demonstrate that in vivo the endothelial transcriptional profile of a coronary artery (the right coronary artery) is intrinsically different from that of a major conduit vessel (the external iliac artery), and that this difference is consistent with former vessel being more prone to atherosclerosis. Keywords: coronary atherosclerosis, endothelial heterogeneity, microarray, gene expression Endothelial cells were freshly harvest from right coronary, left and right iliac arteries from four pigs. RNA were isolated and expression profiles were obtained using olig microarrays.

2010-06-20 | E-GEOD-10938 | biostudies-arrayexpress

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