Cellular and molecular landscape of mammalian sinoatrial node revealed by single-cell RNA sequencing

Dandan Liang, Jinfeng Xue, Li Geng, Liping Zhou, Bo Lv, Qiao Zeng, Ke Xiong, Huixing Zhou, Duanyang Xie, Fulei Zhang, Jie Liu, Yi Liu, Li Li, Jian Yang, Zhigang Xue () and Yi-Han Chen ()
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Dandan Liang: Tongji University School of Medicine
Jinfeng Xue: Tongji University School of Medicine
Li Geng: Tongji University School of Medicine
Liping Zhou: Tongji University School of Medicine
Bo Lv: Tongji University School of Medicine
Qiao Zeng: Tongji University School of Medicine
Ke Xiong: Tongji University School of Medicine
Huixing Zhou: Tongji University School of Medicine
Duanyang Xie: Tongji University School of Medicine
Fulei Zhang: Tongji University School of Medicine
Jie Liu: Tongji University School of Medicine
Yi Liu: Tongji University School of Medicine
Li Li: Tongji University School of Medicine
Jian Yang: Tongji University School of Medicine
Zhigang Xue: Tongji University School of Medicine
Yi-Han Chen: Tongji University School of Medicine

Nature Communications, 2021, vol. 12, issue 1, 1-15

Abstract: Abstract Bioelectrical impulses intrinsically generated within the sinoatrial node (SAN) trigger the contraction of the heart in mammals. Though discovered over a century ago, the molecular and cellular features of the SAN that underpin its critical function in the heart are uncharted territory. Here, we identify four distinct transcriptional clusters by single-cell RNA sequencing in the mouse SAN. Functional analysis of differentially expressed genes identifies a core cell cluster enriched in the electrogenic genes. The similar cellular features are also observed in the SAN from both rabbit and cynomolgus monkey. Notably, Vsnl1, a core cell cluster marker in mouse, is abundantly expressed in SAN, but is barely detectable in atrium or ventricle, suggesting that Vsnl1 is a potential SAN marker. Importantly, deficiency of Vsnl1 not only reduces the beating rate of human induced pluripotent stem cell - derived cardiomyocytes (hiPSC-CMs) but also the heart rate of mice. Furthermore, weighted gene co-expression network analysis (WGCNA) unveiled the core gene regulation network governing the function of the SAN in mice. Overall, these findings reveal the whole transcriptome profiling of the SAN at single-cell resolution, representing an advance toward understanding of both the biology and the pathology of SAN.

Date: 2021
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DOI: 10.1038/s41467-020-20448-x

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