Figshare, Год журнала: 2023, Номер unknown
Опубликована: Янв. 1, 2023
Additional file 7: Table S6. Result SNEEP Per GWAS.
Язык: Английский
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
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
Nature Cardiovascular Research, Год журнала: 2023, Номер 2(10), С. 881 - 898
Опубликована: Окт. 12, 2023
Язык: Английский
Процитировано
6
Heart Rhythm, Год журнала: 2024, Номер 21(11), С. 2320 - 2329
Опубликована: Май 13, 2024
Язык: Английский
Процитировано
1
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
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
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
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
Figshare, Год журнала: 2023, Номер unknown
Опубликована: Янв. 1, 2023
Additional file 3: Table S2. Associated Genes.
Язык: Английский
Процитировано
0
Figshare, Год журнала: 2023, Номер unknown
Опубликована: Янв. 1, 2023
Additional file 4: Table S3. Disease Enrichment Noncoding.
Язык: Английский
Процитировано
0