Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

E11.5 Hand1 myocardial knockout RNA-Seq

ABSTRACT: Aims: To examine the role of the basic Helix-loop-Helix (bHLH) transcription factor HAND1 in embryonic and adult myocardium. Methods and Results: Hand1 is expressed within the cardiomyocytes of the left ventricle (LV) and myocardial cuff between embryonic days (E) 9.5-13.5. Hand gene dosage plays an important role in ventricular morphology and the contribution of Hand1 to congenital heart defects requires further interrogation. Conditional ablation of Hand1 was carried out using either Nkx2.5 knockin Cre (Nkx2.5Cre) or a-myosin heavy chain Cre (aMhc-Cre) driver. Interrogation of transcriptome data via Ingenuity Pathway Analysis (IPA) reveals several gene regulatory pathways disrupted including translation and cardiac hypertrophy-related pathways. Embryo and adult hearts were subjected to histological, functional and molecular analyses. Myocardial deletion of Hand1 results in morphological defects that include cardiac conduction system defects, survivable interventricular septal defects (VSDs), and abnormal LV papillary muscles (PM). Resulting Hand1 conditional mutants are born at Mendelian frequencies; but the morphological alterations acquired during cardiac development result in, the mice developing diastolic heart failure. Conclusions: Collectively, these data reveal that Hand1 contributes to the morphogenic patterning and maturation of cardiomyocytes during embryogenesis and although survivable, indicate a role for Hand1 conduction system and papillary morphogenesis.

ORGANISM(S): Mus musculus

PROVIDER: GSE128571 | GEO | 2019/06/01

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Single-cell RNA sequencing analysis of mouse cardiac tissues with myocardial infarction

Project description:To investigate the transcriotome alteration in myocardial infarction (MI)-associated cells, we performed RNA sequcening analysis with single cells derived from mouse infarcted cardiac tissues or normal left ventricle (LV). Particularly, cardiac endothelial cells (ECs) were traced using a Cdh5-Cre;LSL-tdTomatom system.

2022-03-01 | GSE163956 | GEO

Deletion of Nkx2-5 in trabecular myocardium reveals the developmental origins of pathological heterogeneity associated with ventricular non-compaction cardiomyopathy

Project description:Left ventricular non-compaction (LVNC) is a rare cardiomyopathy associated with a hypertrabeculated phenotype and a large spectrum of symptoms. The developmental origins and mechanistic basis of varying severity of this pathology are unknown. To investigate these issues, we inactivated the cardiac transcription factor Nkx2-5 in trabecular myocardium at different stages of trabecular morphogenesis. Conditional deletion of Nkx2-5 at embryonic stages, during trabecular formation, provokes a severe hypertrabeculated phenotype associated with subendocardial fibrosis and Purkinje fiber hypoplasia. A milder phenotype was observed after Nkx2-5 deletion at fetal stages, during trabecular compaction. A longitudinal study of cardiac function in adult Nkx2-5 conditional mutant mice demonstrates that excessive trabeculation is associated with complex ventricular conduction defects, progressively leading to strain defects, and, in 50% of mutant mice, to heart failure. Progressive impaired cardiac function correlates with conduction and strain defects independently of the degree of hypertrabeculation. Transcriptomic analysis of molecular pathways reflects myocardial remodeling with a larger number of differentially expressed genes in the severe versus mild phenotype and identifies Six1 as a marker upregulated in hypertrabeculated hearts. Our results provide insights into the etiology of LVNC and link its pathogenicity with compromised trabecular development including compaction defects and ventricular conduction system hypoplasia.

2018-04-18 | GSE113251 | GEO

Gene expression analysis of cardiac left-ventricle tissue from hybrid mice harboring the Scn5a-1798insD/+ mutation

Project description:Prolonged electrocardiographic indices reflecting myocardial impulse conduction and repolarization are risk factors for sudden cardiac death and drug-induced arrhythmia. The PR-interval, QRS-duration and QT-interval are heritable traits influenced by multiple genetic and environmental factors. The genetic underpinnings of these traits are still largely unknown. In this study, we leveraged the variability in cardiac gene expression and the variation in PR-, QRS- and QT-intervals among F2 mice harboring the cardiac sodium ion-channel mutation Scn5a-1798insD/+ derived from the 129P2-Scn5a1798insD/+ and FVB/NJ-Scn5a1798insD/+ cross, to isolate novel genes and biological pathways impacting on cardiac conduction and repolarization. Cardiac left-ventricle total RNA from 120 F2-(129P2xFVBN/J)-Scn5a-1798insD/+ mice at 12 to 14 weeks old.

2012-12-01 | E-GEOD-27236 | biostudies-arrayexpress

Infiltrating Monocytes Drive Cardiac Dysfunction in a Cardiomyocyte-Restricted Model of SARS-CoV-2 Infection

Project description:Cardiovascular manifestations of COVID-19 include myocardial injury, heart failure, and myocarditis and are associated with long-term disability and mortality. SARS-CoV-2 RNA and antigens are found in the myocardium of COVID-19 patients, and human cardiomyocytes are susceptible to infection in cell or organoid cultures. While these observations raise the possibility that cardiomyocyte infection may contribute to the cardiac sequelae of COVID-19, a causal relationship between cardiomyocyte infection and myocardial dysfunction and pathology has not been established. Here, we generated a mouse model of cardiomyocyte-restricted infection by selectively expressing human angiotensin converting enzyme 2 (hACE2), the SARS-CoV-2 receptor, in cardiomyocytes. Inoculation of Myh6-Cre Rosa26LSL-hAce2 mice with SARS-CoV-2 resulted in viral replication within the heart, accumulation of macrophages, and moderate left ventricular (LV) systolic dysfunction. Cardiac pathology in this model was transient and resolved with viral clearance. Blockade of monocyte trafficking reduced myocardial viral replication and macrophage accumulation and suppressed the development of LV systolic dysfunction. These findings establish a mouse of model of SARS-CoV-2 cardiomyocyte infection that recapitulates features of cardiac dysfunctions of COVID-19 and suggests that both replication and resultant innate immune responses contribute to pathology

2023-12-31 | GSE239372 | GEO

Cardiac conduction system regeneration prevents arrhythmias after myocardial infarction

Project description:Cardiac conduction system regeneration prevents arrhythmias after myocardial infarction

| PRJNA1030318 | ENA

Identifying gene expression profiles in hypoplastic left heart syndrome and age-matched normal controls

Project description:Affymetrix GeneChip Exon-1.0ST was used to study the differential gene profiles in RV (right ventricle) samples from neonates with HLHS (hypoplastic left heart syndrome) versus RV and LV (left ventricle) samples obtained from age-matched controls. Although few significant changes were observed in the genetic profiles between control LV and control RV, many genes passed the false discovery rate in comparing HLHS-RV to RV and LV control groups, with greater differential profiles noted between HLHS-RV and control RV. Myocardial samples were isolated from the RV of 6 HLHS neonates, diagnosed based upon clinical features including hypoplasia/atresia of the ascending aorta, various degrees of underdevelopment of the aortic valve, mitral valve, and LV cavity, and retrograde flow in the aortic arch as determined by conventional 2-D echocardiography. The mean gestational age at birth of all subjects was 38 weeks (range 36-39) and the mean body weight at surgery of 2.7 kg (range 2.1-3.4 kg) (3 males, 3 females). All subjects were undergoing stage 1 Norwood reconstruction. Children with HLHS and other complex cardiac anomalies entailing non-HLHS single ventricle circulation were excluded from our study. For control samples, RV and LV myocardial tissue was obtained from 5 newborns aged between 1-28 days (mean 18 days; 3 males and 2 females) with normal cardiac anatomy and expired from non-cardiac diseases processes.

2011-12-31 | E-GEOD-23959 | biostudies-arrayexpress

Gene expression analysis of cardiac left-ventricle tissue from hybrid mice harboring the Scn5a-1798insD/+ mutation

2012-12-01 | GSE27236 | GEO

Transcriptomics of cardiac biopsies reveals differences in patients with or without diagnostic parameters for heart failure with preserved ejection fraction

Project description:Heart failure affects 2–3% of adult Western population. Prevalence of heart failure with preserved left ventricular (LV) ejection fraction (HFpEF) increases. Studies suggest HFpEF patients to have altered myocardial structure and functional changes such as incomplete relaxation and increased cardiac stiffness. We hypothesised that patients undergoing elective coronary bypass surgery (CABG) with HFpEF characteristics will show distinctive gene expression compared to patients with normal LV physiology. Myocardial biopsies for mRNA expression analysis were obtained from sixteen patients with LV ejection fraction ≥ 45%. Five out of 16 patients (31%) had echocardiographic characteristics and increased NTproBNP levels indicative of HFpEF and this group was used as HFpEF proxy, while 11 patients had Normal LV physiology. Utilising principal component analysis, the gene expression data clustered into two groups, corresponding to HFpEF proxy and Normal physiology, and 743 differentially expressed genes were identified. The associated top biological functions were cardiac muscle contraction, oxidative phosphorylation, cellular remodelling and matrix organisation. Our results also indicate that upstream regulatory events, including inhibition of transcription factors STAT4, SRF and TP53, and activation of transcription repressors HEY2 and KDM5A, could provide explanatory mechanisms to observed gene expression differences and ultimately cardiac dysfunction in the HFpEF proxy group. <br> Sequencing data from clinical patients fall under GDPR regulations of sharing of personal data and will be made available through EGA-SE.

2019-03-02 | E-MTAB-7454 | biostudies-arrayexpress

Genetics of Myocardial Interstitial Fibrosis in the Human Heart and Association with Disease

Project description:Myocardial interstitial fibrosis is a common thread in multiple cardiovascular diseases including heart failure, atrial fibrillation, conduction disease and sudden cardiac death. To investigate the biologic pathways that underlie interstitial fibrosis in the human heart, we developed a machine learning model to measure myocardial T1 time, a marker of myocardial interstitial fibrosis, in 41,505 UK Biobank participants. Greater T1 time was associated with diabetes mellitus, renal disease, aortic stenosis, cardiomyopathy, heart failure, atrial fibrillation, conduction disease and rheumatoid arthritis. Mendelian randomization analysis supported a potential causal role for diabetes mellitus type 1 in myocardial interstitial fibrosis. In genome-wide association analysis, we identified 11 independent loci associated with native myocardial T1 time. The identified loci implicated genes involved in glucose transport (SLC2A12), iron homeostasis (HFE, TMPRSS6), tissue repair (ADAMTSL1, VEGFC), oxidative stress (SOD2), cardiac hypertrophy (MYH7B) and calcium signaling (CAMK2D). Transcriptome-wide association studies highlighted the role of expression of ADAMTSL1 and SLC2A12 in human cardiac tissue in modulating myocardial interstitial fibrosis. Using a TGFβ1-mediated cardiac fibroblast activation assay, we found that 9 out of the 11 genome-wide significant loci comprised genes that exhibited temporal changes in expression and/or open chromatin conformation supporting the biological relevance of these loci to myocardial fibrosis and myofibroblast cell state acquisition. Harnessing machine learning to perform large-scale phenotyping of interstitial fibrosis in the human heart, our results yield novel insights into biologically relevant pathways to myocardial fibrosis and prioritize a number of pathways for further investigation.

2023-03-11 | GSE225336 | GEO

RNA sequencing analysis of mouse cardiac endothelial cells in myocardial infarction tissues

Project description:To investigate the transcriotome alteration in endothelial cells (ECs) under a myocardial infarction (MI) condition, we performed RNA sequcening analysis with sorted ECs derived from mouse infarcted cardiac tissues or normal left ventricle (LV).

2021-12-31 | GSE163772 | 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