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Cellular Heterogeneity Analysis of the Sinoatrial Node Region Identifies Novel His-bundle-like Cell and Endothelial Progenitor Subtypes

ABSTRACT: Aims: To gain insight into heterogeneity of pacemaker and conduction cells within the sinoatrial node (SAN) and characterize the transcriptome of cardiac endothelial cells (ECs) at single-cell resolution. Methods and results: Single-cell transcriptome analysis of fluorescence activated cell sorting (FACS)-purified SAN cells and surrounding atrial cells from HCN4-GFP knockin mice at postnatal day 2 were performed. Subcluster analysis of SAN cardiomyocyte cluster identified three HCN4+ cell subtypes, including pacemaker cells (PCs), recently identified transitional cells (TCs), and a novel population of His-like conduction cells marked by His-bundle specific marker genes. We additionally refined the molecular signatures of PCs and TCs, and identified Vsnl1, Myl2 and Kcne1 as biomarkers of PCs, TCs and His-like respectively that persistently expressed in the SAN from E15.5 to adult. Furthermore, we observed three endothelial progenitor subtypes (endocardial progenitors, coronary vascular endothelial progenitors, and transitional endothelium migrated from endocardium to coronary vessels) in mouse heart and human fetal heart. These endothelial progenitor subtypes were further identified by mouse lineage tracing analysis. Conclusion: Our study provides a more comprehensive understanding of molecular and cellular signatures underlying pacemaking and conduction of the SAN, and offers new insight into lineage differentiation and diversification of cardiac ECs.

ORGANISM(S): Mus musculus

PROVIDER: GSE182692 | GEO | 2022/08/18

REPOSITORIES: GEO

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A single cell transcriptional roadmap of human pacemaker cell differentiation

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2022-09-01 | GSE189782 | GEO

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2015-07-24 | E-GEOD-69097 | biostudies-arrayexpress

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Genome-wide mRNA expression analyses revealed dysregulation of genes important for SAN function in Hcn4-CreERT2;Isl1 mutants.

2015-07-24 | GSE69097 | GEO

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2015-02-06 | GSE65658 | GEO

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2015-07-23 | E-GEOD-68974 | biostudies-arrayexpress

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