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Sinus venosus adaptation models prolonged cardiovascular disease and reveals insights into evolutionary transitions of the vertebrate heart

ABSTRACT: How two-chambered hearts in basal vertebrates have evolved from single-chamber hearts found in ancestral chordates remains unclear. Here, we show that the teleost sinus venosus (SV) is a chamber-like vessel comprised of an outer layer of smooth muscle cells. We find that in adult zebrafish nr2f1a mutants, which lack atria, the SV comes to physically resemble the thicker bulbus arteriosus (BA) at the arterial pole of the heart through an adaptive, hypertensive response involving smooth muscle proliferation due to aberrant hemodynamic flow. Single cell transcriptomics show that smooth muscle and endothelial cell populations within the adapting SV also take on arterial signatures. Bulk transcriptomics of the blood sinuses flanking the tunicate heart reinforce a model of greater equivalency in ancestral chordate BA and SV precursors. Our data simultaneously reveal that secondary complications from congenital heart defects can develop in adult zebrafish similar to those in humans and that the foundation of equivalency between flanking auxiliary vessels may remain latent within basal vertebrate hearts.

ORGANISM(S): Ciona robusta

PROVIDER: GSE195549 | GEO | 2023/08/19

REPOSITORIES: GEO

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Sinus venosus adaptation models prolonged cardiovascular disease and reveals insights into evolutionary transitions of the vertebrate heart

Project description:How two-chambered hearts in basal vertebrates have evolved from single-chamber hearts found in ancestral chordates remains unclear. Here, we show that the teleost sinus venosus (SV) is a chamber-like vessel comprised of an outer layer of smooth muscle cells. We find that in adult zebrafish nr2f1a mutants, which lack atria, the SV comes to physically resemble the thicker bulbus arteriosus (BA) at the arterial pole of the heart through an adaptive, hypertensive response involving smooth muscle proliferation due to aberrant hemodynamic flow. Single cell transcriptomics show that smooth muscle and endothelial cell populations within the adapting SV also take on arterial signatures. Bulk transcriptomics of the blood sinuses flanking the tunicate heart reinforce a model of greater equivalency in ancestral chordate BA and SV precursors. Our data simultaneously reveal that secondary complications from congenital heart defects can develop in adult zebrafish similar to those in humans and that the foundation of equivalency between flanking auxiliary vessels may remain latent within basal vertebrate hearts.

2023-08-16 | GSE229821 | GEO

Sinus venosus adaptation models prolonged cardiovascular disease and reveals insights into evolutionary transitions of the vertebrate heart

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Sinus venosus adaptation models prolonged cardiovascular disease and reveals insights into evolutionary transitions of the vertebrate heart

2023-04-12 | GSE196307 | GEO

Expression of candidate genes associated with congenital heart disease in adult human atrial and ventricular tissue

Project description:We have used single nuclei RNAseq technology to analyze the expression of four candidate genes (MACROD2, GOSR2, WNT3, MSX1) in right atria and interventicular samples of adult human hearts. We find a robust expression of MACROD2 in all adult cardiac cell types. In contrast, expression of GOSR2 could not be detected in any cell of the adult human heart. WNT3 was sporadically expresssed in fibroblasts, epi- and andocardial cells, smooth muscle cells and cardiomyocytes. MSX1 expression shows a similar isolated expression, except that it is not found in smooth muscle cells and cardiomyocytes.

2022-09-30 | GSE161016 | GEO

Characterization of the effect of deleting the Nrg-1(neuregulin-1) gene, using the endothelial driver line Tie2-Cre in E (embryonic day) 9.5 hearts

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Transcriptional profiling of basilar artery and basilar terminus intima and media in rabbits after bilateral carotid ligation

Project description:New Zealand white rabbits underwent bilateral carotid ligation to increase flow in the basilar artery (BA) or sham surgery. 24 hours post-surgery, the BA and basilar terminus (BT) were embedded for sectioning. The intima and media were separately laser-microdissected from the sections, and whole transcriptome RNA-seq was performed on each tissue in order to more thoroughly characterize potential molecular signals between endothelium and smooth muscle during flow-induced arterial remodeling.

2021-07-28 | GSE169276 | GEO

Transcription profiling of mouse Kir6.1-deficient heart following LPS challenge

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2008-06-15 | E-GEOD-7605 | biostudies-arrayexpress

Total Proteomics of SARS-CoV-2 variants

Project description:The ancestral SARS-CoV-2 strain that initiated the Covid-19 pandemic at the end of 2019 has rapidly mutated into multiple variants of concern with variable pathogenicity and increasing immune escape strategies. However, differences in host cellular antiviral responses upon infection with SARS-CoV-2 variants remains elusive. Leveraging whole cell proteomics, we determined host signalling pathways that are differentially modulated upon infection with the clinical isolates of the ancestral SARS-CoV-2 B.1 and the variants of concern Delta and Omicron BA.1. Our findings illustrate alterations in the global host proteome landscape upon infection with SARS-CoV-2 variants and the resulting host immune responses. Additionally, viral proteome kinetics reveal declining levels of viral protein expression during Omicron BA.1 infection when compared to ancestral B.1 and Delta variants, consistent with its reduced replication rates. Moreover, molecular assays reveal deferral activation of specific host antiviral signalling upon Omicron BA.1 and BA.2 infection. Our study provides an overview of host proteome profile of multiple SARS-CoV-2 variants and brings forth a better understanding of the instigation of key immune signalling pathways causative for the differential pathogenicity of SARS-CoV-2 variants.

2023-05-10 | PXD037265 | Pride

Regional differences in mRNA and lncRNA expression patterns in the non-failing human heart

Project description:Background: Although chamber specialization is critical for proper cardiac function, a comprehensive, genome-wide analysis of the cardiac transcriptome, including identification of regional differences in mRNA and lncRNA expression patterns for the four chambers and interventricular septum of the non-failing human heart, has not been performed. Methods and Results: mRNA and long noncoding RNA (lncRNA) transcriptional profiling of the left (LA) and right (RA) atria, left (LV) and right (RV) ventricles, and the interventricular septum (IVS) of non-failing human hearts (N=8) was performed by deep sequencing. Analysis of the mRNA and lncRNA expression profiles revealed that the different regions of the heart are distinct. Differential expression analysis of paired tissue samples identified 5,747 mRNAs and 2,794 lncRNAs with chamber-enriched expression patterns. The largest differences in mRNA and lncRNA expression were evident between atria and ventricular samples, including regional differences in ~20% of all cardiac expressed mRNA and lncRNA transcripts. Regional differences in mRNA and lncRNA expression were also evident, although to a lesser extent, between the LA and RA, and between the LV, RV and IVS. Gene ontology classification of differentially expressed gene sets revealed regional differences in chamber specialization, including differences in signaling, metabolism, and muscle contraction. Sex differences in mRNA and lncRNA gene expression profiles were also identified between male and female LA and RA samples. Conclusions: There are marked regional differences in the mRNA and lncRNA expression profiles in non-failing adult human heart, and are associated with chamber specialization.

2018-10-16 | GSE112339 | GEO

Preparation of chimeric recombinant SARS-CoV-2

Project description:To investigate the virological properties of a SARS-CoV-2 variant, Omicron BA.2, we generated chimeric recombinant viruses that express GFP and encodes the S gene of B.1.1 (ancestral D614G-bearing virus), Delta, BA.1 and BA.2. To verify the genome sequence of the working viruses, we performed viral RNA-sequencing of the viral stock.

2022-02-16 | GSE196649 | GEO

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