Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

The role of SMC3 in heart development by regulating super-enhancer associated genes

ABSTRACT: Abnormal cardiac development has been observed in individuals with Cornelia de Lange Syndrome (CdLS) due to mutations in genes encoding members of the cohesin complex. But the precise role of cohesin in heart development remains elusive. In this study, we aimed to elucidate the indispensable role of SMC3, a component of the cohesin complex, in cardiac development and its underlying mechanism. Our investigation revealed an association between SMC3 mutations and congenital heart disease (CHD) in CdLS patients. To further explore this relationship, we utilized heart-specific Smc3-knockout (SMC3-cKO) mice, which displayed varying degrees of outflow tract (OFT) abnormalities. Additionally, we identified 16 rare SMC3 variants with potential pathogenicity in individuals with isolated CHD. Employing single nucleus RNA sequencing and 3C-high-throughput genome-wide translocation sequencing, we unveiled that Smc3 deletion downregulates the expression of key genes, including Ets2, in OFT cardiac muscle cells by specifically decreasing interactions between super-enhancers (SE) and promoters. Notable, Ets2-SE-null mice also exhibit delayed OFT development in the heart. Our research uncovers a novel role for SMC3 in heart development by regulating SE-associated genes, suggesting its potential relevance as one of the CHD-related genes and providing crucial insights into the molecular basis of cardiac development.

ORGANISM(S): Mus musculus

PROVIDER: GSE242974 | GEO | 2023/09/14

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

A multi-omics approach using a mouse model of cardiac malformations for prioritization of human congenital heart disease contributing genes [scRNA-seq]

Project description:Congenital heart disease (CHD) is the most common type of birth defect, affecting ~1% of all live births. Malformations of the cardiac outflow tract (OFT) account for ~30% of all CHD and include a range of CHDs from bicuspid aortic valve (BAV) to tetralogy of Fallot (TOF). We hypothesized that transcriptomic profiling of a mouse model of CHD would highlight disease-contributing genes implicated in congenital cardiac malformations in humans. To test this hypothesis, we utilized global transcriptional profiling differences from a mouse model of OFT malformations to prioritize damaging, de novo variants identified from exome sequencing datasets from published cohorts of CHD patients. Notch1+/-;Nos3-/- mice display a spectrum of cardiac OFT malformations ranging from BAV, semilunar valve (SLV) stenosis to TOF. Global transcriptional profiling of the E13.5 Notch1+/-;Nos3-/- mutant mouse OFTs and wildtype controls was performed by RNA sequencing (RNA-Seq). Analysis of the RNA-Seq dataset demonstrated genes belonging to the Hif1α, Tgf-β, Hippo, and Wnt signaling pathways were differentially expressed in the mutant OFT. Mouse to human comparative analysis was then performed to determine if patients with TOF and SLV stenosis display an increased burden of damaging, genetic variants in gene homologs that were dysregulated in Notch1+/-; Nos3-/- OFT. We found an enrichment of de novo variants in the TOF population among the 1,352 significantly differentially expressed genes in Notch1+/-;Nos3-/- mouse OFT but not the SLV population. This association was not significant when compared to only highly expressed genes in the murine OFT and of de novo variants in the TOF population. These results suggest that transcriptomic datasets generated from the appropriate temporal, anatomic and cellular tissues from murine models of CHD may provide a novel approach for the prioritization of disease-contributing genes in patients with CHD.

2021-06-28 | GSE171238 | GEO

A multi-omics approach using a mouse model of cardiac malformations for prioritization of human congenital heart disease contributing genes [RNA-seq]

2021-06-28 | GSE171237 | GEO

Impaired Cohesin Loading in Cornelia de Lange Syndrome Results in a Highly Specific Pattern of Dysregulated Genes

Project description:Heterozygous mutations in the cohesin regulator, NIPBL, or cohesin structural components SMC1A, and SMC3, result in Cornelia de Lange Syndrome (CdLS). Genome-wide transcription assessment has identified unique profiles of genes dysregulated in CdLS that correlate with different clinical presentations. Cohesin binding analysis demonstrates a preference for intergenic regions suggesting a cis-regulatory function mimicking that of an insulator. However, the binding sites are enriched within the promoter regions of the dysregulated genes and are significantly decreased in CdLS probands, indicating an alternative role of cohesin as a classic transcription factor. Keywords: ChIP-chip

2009-05-28 | GSE12603 | GEO

Elevated microRNA-187 causes cardiac endothelial dysplasia to promote congenital heart disease through inhibition of NIPBL [ATAC-seq Heart]

Project description:Dysplasia of cardiac endothelial cells significantly contributes to congenital heart disease (CHD), the most common congenital disability. The regulatory role of miRNAs in this process remains elusive. This study identified elevated miR-187 expression in embryonic heart endothelial cells from CHD fetuses. Using a conditional knock-in model, we showed that increased miR-187 levels in embryonic endothelial cells induce CHD in homozygous fetal mice, closely mirroring human CHD. Mechanistically, miR-187 targets NIPBL, which is responsible for recruiting the cohesin complex and facilitating chromatin accessibility between enhancers and promoters. Consequently, the endothelial cell-specific upregulation of miR-187 inhibited NIPBL, leading to reduced chromatin accessibility and impaired gene expression, which hindered endothelial cell development and ultimately caused heart septal defects and reduced heart size both in vitro and in vivo. Importantly, exogenous miR-187 expression in human cardiac organoids mimicked developmental defects in the cardiac endothelial cells, reversible by NIPBL replenishment. Our findings establish the miR-187/NIPBL axis as a potent regulator that inhibits cardiac endothelial cell development by attenuating the transcription of numerous endothelial genes, with our mouse and human cardiac organoid models effectively replicating severe defects from minor perturbations.

2024-11-03 | GSE276222 | GEO

Elevated microRNA-187 causes cardiac endothelial dysplasia to promote congenital heart disease through inhibition of NIPBL [ATAC-Seq]

2024-11-03 | GSE276221 | GEO

Elevated microRNA-187 causes cardiac endothelial dysplasia to promote congenital heart disease through inhibition of NIPBL

2024-11-03 | GSE275951 | GEO

Elevated microRNA-187 causes cardiac endothelial dysplasia to promote congenital heart disease through inhibition of NIPBL [Heart RNA-Seq]

2024-11-03 | GSE275950 | GEO

Elevated microRNA-187 causes cardiac endothelial dysplasia to promote congenital heart disease through inhibition of NIPBL [CUT&Tag]

2024-11-03 | GSE275850 | GEO

Elevated microRNA-187 causes cardiac endothelial dysplasia to promote congenital heart disease through inhibition of NIPBL [Endothelial cell RNA-seq]

2024-11-03 | GSE275849 | GEO

Transcription profile of hearts extracted from zebrafish embryos treated with SU5402 at 48 hpf

Project description:Heart formation requires input from two populations of progenitor cells - the first and second heart fields - that differentiate at distinct times and create different cardiac components. The cardiac outflow tract (OFT) is built through recruitment of late-differentiating, second heart field (SHF) -derived cardiomyocytes to the arterial pole of the heart. Mechanisms responsible for selection of an appropriate number of OFT cells from the SHF remain unclear, although several lines of evidence emphasize the importance of FGF signaling in promoting this process. Here, we examine the impact of inhibition of FGF signaling on cardiac transcription profiles in an effort to identify genes operating downstream of FGF during OFT development.

2014-05-12 | GSE55540 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data