Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Single-cell TCR Profiling in Left Atria Identifies Complement Pathway Involvement in Atrial Fibrillation

ABSTRACT: Atrial fibrillation (AF) is the most prevalent arrhythmia and is strongly associated with stroke, heart failure, and increased mortality. However, the role of T cells in AF pathogenesis remains unclear. In this study, we aimed to characterize the detailed landscape and clonal expansion of T cells using single-cell TCR sequencing, and validate our findings via O-link proteomics in plasma. Analysis of left atrial tissues from eight AF patients identified five CD4+ T cells, six CD8+ T cells, and gamma delta T cells based on canonical gene expression markers. Notably, we observed clonal expansion of resident memory and cytotoxic T cells. CellChat analysis highlighted complement signaling–mediated interactions between T cells and fibroblasts. Furthermore, proteomics in plasma using the Olink platform confirmed enriched complement activation in non-paroxysmal AF compared to paroxysmal AF. These findings suggest that activation of complement pathway between T cells and fibroblasts contributes to atrial remodeling and may serve as a potential therapeutic target for AF.

ORGANISM(S): Homo sapiens

PROVIDER: GSE294456 | GEO | 2026/04/01

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Transcriptome and Proteome Mapping in the Sheep Atria Reveal Molecular Features of Atrial Fibrillation Progression

Project description:Atrial fibrillation (AF) is often a progressive cardiac arrhythmia that increases the risk of hospitalization and adverse cardiovascular events. There is a clear demand for more inclusive and large-scale approaches to understand the molecular drivers responsible for AF, as well as the fundamental mechanisms governing the transition from paroxysmal to persistent and permanent forms. We aimed to create a molecular map of AF and find the distinct genetic programs underlying cell type-specific atrial remodeling and AF progression. We used a sheep model of long-standing, tachypacing-induced AF, sampled right and left atrial tissue and isolated cardiomyocytes from control, intermediate (transition) and late time points during AF progression, and performed transcriptomic and proteome profiling. We have merged all these layers of information into a meaningful 3-component space in which we explored the genes and proteins detected and their common patterns of expression. Our data-driven analysis points at extracellular matrix remodeling, inflammation, ion channel, myofibril structure, mitochondrial complexes and chromatin remodeling as hallmarks of AF progression. Most important, we prove that these changes occur at early transitional stages of the disease, but not at later stages, and that the left atrium undergoes significantly more profound changes than the right atrium in its expression program. The pattern of dynamic changes in gene and protein expression correspond closely with the electrical and structural remodeling demonstrated previously in the sheep and in humans. The results provide novel insight into the dynamics of gene and protein expression changes that underlie AF-induced atrial remodeling and that make the arrhythmia become more stable and long lasting.

2021-01-08 | PXD015637 | Pride

Reduced left atrial cardiomyocyte PITX2 and elevated circulating BMP10 predict atrial fibrillation after ablation

Project description:Background: Genomic and experimental studies suggest a role for PITX2 in atrial fibrillation (AF). To assess whether this association is relevant for recurrent AF in patients, we tested whether left atrial PITX2 affects recurrent AF after AF ablation. Methods: mRNA concentrations of PITX2 and its cardiac isoform, PITX2c, were quantified in left atrial appendages (LAA) from patients undergoing thoracoscopic AF ablation, either in whole LAA tissue (n=83) or in LAA cardiomyocytes (n=52), and combined with clinical parameters to predict AF recurrence. Literature suggests bone morphogenetic protein 10 (BMP10) as a PITX2-repressed, atrial-specific, secreted protein. BMP10 plasma concentrations were combined with eleven cardiovascular biomarkers and clinical parameters to predict recurrent AF after catheter ablation in 359 patients. Results: Reduced cardiomyocyte PITX2 concentrations, but not whole LAA tissue PITX2, were associated with AF recurrence after thoracoscopic AF ablation (16% decreased recurrence per 2-(ΔΔCt) increase in PITX2). RNA sequencing, qPCR and Western blotting confirmed BMP10 as one of most PITX2-repressed atrial genes. Left atrial size (hazard ratio per mm increase, HR [95%CI] 1.055 [1.028, 1.082], non-paroxysmal AF (HR 1.672 [1.206, 2.318]) and elevated BMP10 (HR 1.339 [CI 1.159, 1.546] per quartile increase) were predictive of recurrent AF. BMP10 outperformed eleven other cardiovascular biomarkers in predicting recurrent AF. Conclusions: Reduced left atrial cardiomyocyte PITX2 and elevated plasma concentrations of the PITX2-repressed, secreted, atrial protein BMP10 identify patients at risk of recurrent AF after ablation.

2020-06-19 | GSE152181 | GEO

Transcriptome and Proteome Mapping in the Sheep Atria Reveal Molecular Features of Atrial Fibrillation Progression

2020-09-30 | GSE138255 | GEO

Atrial fibrillation is associated with altered left-to-right atria gene expression ratio: implications for arrhythmogenesis and thrombogenesis

Project description:Background: Atrial fibrillation (AF) causes atrial remodeling, and the left atrium (LA) is the favored substrate for maintaining AF. However, it remains unclear if AF remodels both atria differently and contributes to LA arrhythmogenesis and thrombogenesis. Results: AF was associated with differential LA-to-RA gene expression related to specific ion channels and pathways as well as upregulation of thrombogenesis-related genes in the LA appendage. Targeting the molecular mechanisms underlying the LA-to-RA difference and AF-related remodeling in the LA appendage may help provide new therapeutic options in treating AF and preventing thromboembolism in AF. Paired left atrial and right atrial specimens were obtained from 13 patients with persistent AF receiving valvular surgery. The Paired specimens were sent for microarray comparison. Selected results were validated by quantitative real time-PCR (q-PCR) and Western blotting. Ultrastructural changes in the atria were evaluated by immunohistochemistry.

2016-08-09 | E-GEOD-79768 | biostudies-arrayexpress

Atrial fibrillation is associated with altered left-to-right atria gene expression ratio: implications for arrhythmogenesis and thrombogenesis

2016-08-09 | GSE79768 | GEO

Valvular heart disease and atrial fibrillation regulate microRNA expression profiles in left and right atria differently

Project description:Background: Chronic atrial fibrillation (AF) is a complication associated with the dilated atria of patients with valvular heart disease and contributes to worsened pathology. Methods and Results: Using microarray technology, we examined microRNA (miR) expression profiles in right and left atrial appendage tissue from valvular heart disease (VHD) patients. Right atrial appendage from patients undergoing coronary artery bypass grafting (CABG) and left atrial (LA) appendage from healthy hearts not used for transplant were used as controls. VHD induced different changes in miR expression in LA compared with right atria (RA). Fifty-two (52) miRs were altered by VHD in LA, compared with 5 in RA tissue. There was no detectable effect of chronic AF on miR expression in LA tissue, but miR expression in RA was strongly influenced by AF, with 47 miRs showing differential expression. LA volume correlated with miR expression changes in both LA and RA, but the affected miRs were different for the two atrial groups. Conclusions: VHD and AF influence miR expression patterns in LA and RA, but these are affected differently by disease progression and by the development of AF. These findings provide new insights into the progression of VHD. RA tissue is not a useful surrogate for LA in studies of mitral valve disease. 34 arrays from either the left or right atrium from patients with Valvular Heart Disease (VHD), patients undergoing coronary artery bypass grafting (CABG), or healthy controls. Arrays in this series were generated on V2 and V3 Agilent microRNA arrays and analysed in combination.

2011-12-21 | E-GEOD-28954 | biostudies-arrayexpress

Valvular heart disease and atrial fibrillation regulate microRNA expression profiles in left and right atria differently

2011-12-21 | GSE28954 | GEO

High rate triggers increased atrial release of BMP10, a biomarker for atrial fibrillation and stroke, and BMP10 affects ventricular cardiomyocytes

Project description:Background Bone morphogenetic protein 10 (BMP10) is a ligand of the TGFβ superfamily secreted mainly by atrial cardiomyocytes. Elevated BMP10 blood concentrations predict atrial fibrillation (AF), AF recurrence after ablation and AF-related cardiovascular complications like stroke. The conditions increasing BMP10 secretion and downstream effects of BMP10 in cardiomyocytes are poorly understood. We assessed BMP10 secretion dynamics and BMP10 effects in a human 3D model of atrial and ventricular engineered heart tissue (EHT). Methods Cardiomyocytes differentiated from human induced pluripotent stem cells (atrial and ventricular) were cast into a fibrin-matrix to generate EHT. Atrial EHTs were optogenetically paced (3-5 Hz) or maintained at intrinsic beating rate for 24 h up to 15 days. Release of BMP10 and other cardiac biomarkers from EHT were quantified. BMP10 plasma concentrations were compared between 1370 patients in different atrial rhythm at blood draw. Additionally, ventricular EHTs were exposed to BMP10 for 10 days. Results Atrial but not ventricular EHT released BMP10 within 48 h of culture. High rate optogenetic pacing increased atrial EHT BMP10 release by ~3-fold after a latency of at least 24 h post pacing initiation. BMP10 plasma concentrations were elevated in patients with documented AF compared to sinus rhythm and even higher in patients with current AF. BMP10 induced upregulation of TGFβ pathway transcripts, increased expression of genes related to AF and heart failure, including PITX2 and NPPB, and increased relative contraction times in ventricular EHTs. Conclusions High atrial rates elevate BMP10 expression and release, and higher plasma concentrations of BMP10 are observed in patients with active AF. BMP10 exposure induces transcriptomic changes linked to AF and heart failure in ventricular EHT. These findings support BMP10 as a biomarker and potential mediator of AF-related remodeling and tachycardiomyopathy.

2025-10-14 | GSE306533 | GEO

Single Cell Landscape of Left Atria Reveals Amphiregulin and Insulin-like Growth Factor 1 as Surrogate Markers in Patients with Atrial Fibrillation.

Project description:Atrial fibrillation (AF) is strongly associated with strokes, heart failure, and increased mortality. Inflammation plays a role in the pathophysiology of AF; however, how inflammation in AF is sustained and induces fibrosis is unclear. Therefore, this study aimed to identify the characteristic monocyte–macrophage heterogeneity and the cell–cell interactions between immune and non-immune cells at a single cell level in the left atrial (LA) tissues of patients with AF who underwent LA appendectomies. Myeloid cells were divided into five macrophage clusters, TNF+, two IL1B+, TREM2+, LYVE1+ resident macrophages, three monocyte clusters, five dendritic cell clusters, neutrophils, and mast cells. The CellChat analysis revealed that IL1B+ macrophages send epidermal growth factor (EGF) signalling to fibroblasts and resident macrophages send IGF1 singalling to cardiomyocytes. When compared to openly published control samples, Amphiregulin (AREG) was the most upregulated gene in monocytes and monocyte-derived IL1B+ macrophages in the AF group. We also found that AREG levels in serum were higher in patients with AF than controls. EGF signalling from IL1B+ macrophages could be therapeutic targets for AF, and AREG could be a functional biomarker for AF.

2024-06-01 | GSE261170 | GEO

Time-series proteome profiling analysis of the atria in a murine model of angiotensin II-induced atrial fibrillation

Project description:Atrial fibrillation (AF) is the most common form of arrhythmia observed in clinical cardiac diseases. Angiotensin II (Ang II) and elevation of blood pressure have been considered to be the main risk regulators of AF. However, the time series proteome profiling and the key signaling pathways involved in the development of Ang II-induced AF remain unclear. Wild-type C57BL/6 male mice (10 weeks old) were infused with Ang II (2000 ng/kg/min) for 1, 2 and 3 weeks, respectively. AF inducibility, left atrial volume and fibrosis were examined by echocardiography and histological staining. The time series proteome in atria tissues was evaluated with Isobaric tags for relative and absolute quantitation (iTRAQ) and liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) technologies. This study defined the dynamic changes of the differentially expressed proteins (DEPs) involved in Ang II-induced AF, and identified that mitochondrial oxidative phosphorylation may play a key role in this disease. These findings provide a resource for understanding the molecular mechanism research of AF.

2022-04-04 | PXD022238 | Pride

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