Dataset Information

Quantitative proteomics profiling determines the uniqueness of the sinus node

ABSTRACT: The sinus node is a collection of highly specialized cells that constitute the natural pacemaker activity of our heart. The protein expression landscape of the sinus node differs from the surrounding cardiac tissue, although it is primarily comprised of myocytes and fibroblasts like the rest of the cardiac tissue, endowing it with its unique ability to regulate heart rate. Here we performed quantitative proteomics experiments to profile protein expression in the pacemaker of the heart, and compared it to protein expression in the neighbouring atrial muscle. In summary, the quantitative proteomics data presented here offer a highly detailed insight into the unique composition of the pacemaker of our heart.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Heart

SUBMITTER: Nora Linscheid

LAB HEAD: Alicia Lundby

PROVIDER: PXD008736 | Pride | 2019-07-08

REPOSITORIES: Pride

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Publications

Quantitative proteomics and single-nucleus transcriptomics of the sinus node elucidates the foundation of cardiac pacemaking.

Linscheid Nora N Logantha Sunil Jit R J SJRJ Poulsen Pi Camilla PC Zhang Shanzhuo S Schrölkamp Maren M Egerod Kristoffer Lihme KL Thompson Jonatan James JJ Kitmitto Ashraf A Galli Gina G Humphries Martin J MJ Zhang Henggui H Pers Tune H TH Olsen Jesper Velgaard JV Boyett Mark M Lundby Alicia A

Nature communications 20190628 1

The sinus node is a collection of highly specialised cells constituting the heart's pacemaker. The molecular underpinnings of its pacemaking abilities are debated. Using high-resolution mass spectrometry, we here quantify >7,000 proteins from sinus node and neighbouring atrial muscle. Abundances of 575 proteins differ between the two tissues. By performing single-nucleus RNA sequencing of sinus node biopsies, we attribute measured protein abundances to specific cell types. The data reveal signif ...[more]

PMID: 31253831

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Project description:Atrial fibrillation (AF) is the most common sustained arrhythmia characterized by rapid and multiple irregular excitations within the atria. AF is associated with serious morbidity and increased mortality, and its prevalence is prospected to increase as society ages. The limited therapeutic efficacy of AF treatment as well as its high socioeconomic burden makes AF a major clinical challenge. Despite our expanding knowledge of individual proteins and pathways involved in the complex pathophysiology of atrial fibrillation (AF), an unbiased overview of proteins and functionally enriched biological processes as well as their crosstalk is lacking. Here, we performed an explorative proteomics analysis to reveal the global abundance of proteins in cardiac tissue of patients, and deciphered functionally grouped gene ontologies (GO) to uncover a perspective of the disease biology driving or driven by AF. A total of 2703 proteins were identified by liquid chromatography coupled to tandem mass spectrometry. Among them, 150 proteins (accounting for 5.6% of 2703) had a significantly altered abundance (100 proteins increased and 50 decreased) in AF. A significant biological connection was found between those (protein-protein interaction enrichment p-value=1.0e-16). GO enrichment analysis showed that these 150 proteins were mainly located in extracellular/cytoplasmic vesicles, mitochondrion, and cytoskeletal compartments. Correspondingly, the 100 proteins increased in AF were significantly enriched in the GO terms related to immune system, metabolic process, iron process, ECM disassembly, mitochondrial translation and apoptotic signaling. Partially clustered proteins with dense functional link were found in immune system and metabolic process, and were respectively annotated in neutrophil degranulation, and oxoacid metabolic process coupled to the subunits of mitochondrial dehydrogenase NADH. Those processes enriched in AF had crosstalk via the proteins involved in neutrophil degranulation. Selected proteins such as LCN2 (neutrophil degranulation), CA3 (immune system), NDUFS2 (complex I) and MYH10 (actin motor protein) were validated by western blot or qPCR in an independent cohort. The 50 proteins decreased in AF were collectively enriched in vesicle-mediated transport and actin filament-based movement. We demonstrate that important biological processes underlying persistent AF as well as their crosstalk via the components of neutrophil degranulation. Our study provides a novel insight for a more efficient targeting strategy for AF treatment.

Dataset Information

Quantitative proteomics profiling determines the uniqueness of the sinus node

Publications

Quantitative proteomics and single-nucleus transcriptomics of the sinus node elucidates the foundation of cardiac pacemaking.

Similar Datasets

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