Additional file 7 of CVD-associated SNPs with regulatory potential reveal novel non-coding disease genes DOI Creative Commons
Chaonan Zhu, Nina Baumgarten,

Meiqian Wu

и другие.

Figshare, Год журнала: 2023, Номер unknown

Опубликована: Янв. 1, 2023

Additional file 7: Table S6. Result SNEEP Per GWAS.

Язык: Английский

CVD-associated SNPs with regulatory potential reveal novel non-coding disease genes DOI Creative Commons
Chaonan Zhu, Nina Baumgarten,

Meiqian Wu

и другие.

Human Genomics, Год журнала: 2023, Номер 17(1)

Опубликована: Июль 25, 2023

Cardiovascular diseases (CVDs) are the leading cause of death worldwide. Genome-wide association studies (GWAS) have identified many single nucleotide polymorphisms (SNPs) appearing in non-coding genomic regions CVDs. The SNPs may alter gene expression by modifying transcription factor (TF) binding sites and lead to functional consequences cardiovascular traits or diseases. To understand underlying molecular mechanisms, it is crucial identify which variations involved how they affect TF binding. SNEEP (SNP exploration analysis using epigenomics data) pipeline was used regulatory SNPs, behavior TFs link GWAS their potential target genes for six human-induced pluripotent stem cells derived cardiomyocytes (hiPSC-CMs), monoculture cardiac organoids (MCOs) self-organized (SCOs) were study. Gene expression, cardiomyocyte size contractility assessed. By our integrative computational pipeline, we 1905 CVD data. These associated with hundreds genes, half them RNAs (ncRNAs), suggesting novel genes. We experimentally tested 40 CVD-associated RNAs, among RP11-98F14.11, RPL23AP92, IGBP1P1, CTD-2383I20.1, upregulated hiPSC-CMs, MCOs SCOs under hypoxic conditions. Further experiments showed that IGBP1P1 depletion rescued hypertrophic marker reduced hypoxia-induced improved hypoxia-reduced hiPSC-CMs MCOs. a ncRNA key functions modulating function disease models. Our data suggest as therapeutic improve

Язык: Английский

Процитировано

14

Context-dependent T-BOX transcription factor family: from biology to targeted therapy DOI Creative Commons
Siwen Li, Xiangyuan Luo, Mengyu Sun

и другие.

Cell Communication and Signaling, Год журнала: 2024, Номер 22(1)

Опубликована: Июль 4, 2024

Abstract T-BOX factors belong to an evolutionarily conserved family of transcription factors. not only play key roles in growth and development but are also involved immunity, cancer initiation, progression. Moreover, the same molecule exhibits different or even opposite effects various developmental processes tumor microenvironments. Understanding multiple context-dependent malignancies is vital for uncovering potential T-BOX-targeted therapy. We summarize physiological their pathological observed when expression dysregulated. discuss regulatory immune microenvironment (TIME) newly arising questions that remain unresolved. This review will help systematically comprehensively understanding role factor physiology, pathology, immunity. The intention provide valuable information support

Язык: Английский

Процитировано

5

Tbx5 maintains atrial identity in postnatal cardiomyocytes by regulating an atrial-specific enhancer network DOI
Mason Sweat, Yangpo Cao, Xiaoran Zhang

и другие.

Nature Cardiovascular Research, Год журнала: 2023, Номер 2(10), С. 881 - 898

Опубликована: Окт. 12, 2023

Язык: Английский

Процитировано

6

14-3-3ε/YWHAE regulates the transcriptional expression of cardiac sodium channel NaV1.5 DOI
Yushuang Hu, Chi Zhang, Shun Wang

и другие.

Heart Rhythm, Год журнала: 2024, Номер 21(11), С. 2320 - 2329

Опубликована: Май 13, 2024

Язык: Английский

Процитировано

1

Atrial fibrillation variant-to-gene prioritization through cross-ancestry eQTL and single-nucleus multiomic analyses DOI Creative Commons
Francis Leblanc,

Xuexin Jin,

Kai Kang

и другие.

iScience, Год журнала: 2024, Номер 27(9), С. 110660 - 110660

Опубликована: Авг. 5, 2024

Highlights•Bulk and single-nucleus RNA-seq data from human atria help interpret AF GWAS results•Co-localization fine-mapping implicate 14 genes at 9 loci•LINC01629 is involved in the development of atrial tissue conduction systemSummaryAtrial fibrillation (AF) most common arrhythmia world. Human genetics can provide strong therapeutic candidates, but identification causal their functions remains challenging. Here, we applied an strategy that leverages results a previously published cross-ancestry genome-wide association study (GWAS), expression quantitative trait loci (eQTLs) left appendages (LAAs) obtained two cohorts with distinct ancestry, paired RNA sequencing (RNA-seq) ATAC (ATAC-seq) LAA assay (sn-multiome). At nine loci, our co-localization analyses implicated genes. Data integration identified several candidate variants, including rs7612445 GNB4 rs242557 MAPT. Finally, showed repression strongest AF-associated eQTL gene, LINC01629, embryonic stem cell-derived cardiomyocytes using CRISPR inhibition dysregulation pathways linked to cardiac system.Graphical abstract

Язык: Английский

Процитировано

1

Beyond genomic studies of congenital heart defects through systematic modelling and phenotyping DOI Creative Commons
Deborah J. Henderson, Ahlam Alqahtani, Bill Chaudhry

и другие.

Disease Models & Mechanisms, Год журнала: 2024, Номер 17(11)

Опубликована: Ноя. 1, 2024

Congenital heart defects (CHDs), the most common congenital anomalies, are considered to have a significant genetic component. However, despite considerable efforts identify pathogenic genes in patients with CHDs, few gene variants been proven as causal. The complexity of architecture underlying human CHDs likely contributes this poor discovery rate. several other factors contribute. For example, level patient phenotyping required for clinical care may be insufficient research studies focused on mechanistic discovery. Although hundred mouse knockouts described these generally not phenotyped and same way patients, thus readily comparable. Moreover, carry uncertain significance crucial cardiac genes, further complicating comparisons between humans mutants. In spite major advances developmental biology over past 25 years, well communicated geneticists cardiologists. As consequence, latest data from always used design interpretation aimed at discovering causes CHDs. Special Article, while considering vitro vivo models, we create coherent framework accurately modelling mice, thereby enhancing translation genomic into patients.

Язык: Английский

Процитировано

1

Overview of programmed electrical stimulation to assess atrial fibrillation susceptibility in mice DOI Creative Commons
Matthew B. Murphy, Prince J. Kannankeril, Katherine T. Murray

и другие.

Frontiers in Physiology, Год журнала: 2023, Номер 14

Опубликована: Апрель 11, 2023

Atrial fibrillation (AF) is the most common human arrhythmia and associated with increased risk of stroke, dementia, heart failure, death. Among several animal models that have been used to investigate molecular determinants AF, mouse become prevalent due low cost, ease genetic manipulation, similarity disease. Programmed electrical stimulation (PES) using intracardiac or transesophageal atrial pacing induce AF as do not develop spontaneous AF. However, there a lack standardized methodology resulting in numerous PES protocols literature differ respect multiple parameters, including protocol duration, stimulus amplitude, pulse width, even definition Given this complexity, selection appropriate for specific model has arbitrary. Herein we review development PES, commonly protocols, selected experimental models, advantages disadvantages both techniques. We also emphasize detection artifactual induction unintended parasympathetic stimulation, which should be excluded from results. recommend optimal elicit an phenotype individualized acquired factors, analysis definitions endpoint.

Язык: Английский

Процитировано

2

Role of Genetic Variation in Transcriptional Regulatory Elements in Heart Rhythm DOI Creative Commons
Timo Jonker, Phil Barnett, Gerard J.J. Boink

и другие.

Cells, Год журнала: 2023, Номер 13(1), С. 4 - 4

Опубликована: Дек. 19, 2023

Genetic predisposition to cardiac arrhythmias has been a field of intense investigation. Research initially focused on rare hereditary arrhythmias, but over the last two decades, role genetic variation (single nucleotide polymorphisms) in heart rate, rhythm, and taken into consideration as well. In particular, genome-wide association studies have identified hundreds genomic loci associated with quantitative electrocardiographic traits, atrial fibrillation, less common such Brugada syndrome. A significant number variants found systematically localize non-coding regulatory elements that control tissue-specific temporal transcription genes encoding factors, ion channels, other proteins. However, identification causal mechanism underlying their impact phenotype proven difficult due complex tissue-specific, time-resolved, condition-dependent, combinatorial function elements, well modest conservation across different model species. this review, we discuss research efforts aimed at identifying characterizing-trait-associated variant molecular mechanisms rate or rhythm.

Язык: Английский

Процитировано

0

Additional file 3 of CVD-associated SNPs with regulatory potential reveal novel non-coding disease genes DOI Creative Commons
Chaonan Zhu, Nina Baumgarten,

Meiqian Wu

и другие.

Figshare, Год журнала: 2023, Номер unknown

Опубликована: Янв. 1, 2023

Additional file 3: Table S2. Associated Genes.

Язык: Английский

Процитировано

0

Additional file 4 of CVD-associated SNPs with regulatory potential reveal novel non-coding disease genes DOI Creative Commons
Chaonan Zhu, Nina Baumgarten,

Meiqian Wu

и другие.

Figshare, Год журнала: 2023, Номер unknown

Опубликована: Янв. 1, 2023

Additional file 4: Table S3. Disease Enrichment Noncoding.

Язык: Английский

Процитировано

0