Dbh+ catecholaminergic cardiomyocytes contribute to the structure and function of the cardiac conduction system in murine heart

Tianyi Sun, Alexander Grassam-Rowe, Zhaoli Pu, Yangpeng Li, Huiying Ren, Yanru An, Xinyu Guo, Wei Hu, Ying Liu, Yuqing Zheng, Zhu Liu, Kun Kou, Xianhong Ou, Tangting Chen, Xuehui Fan, Yangyang Liu, Shu Tu, Yu He, Yue Ren, Ao Chen, Zhouchun Shang, Zhidao Xia, Lucile Miquerol, Nicola Smart, Henggui Zhang, Xiaoqiu Tan (), Weinian Shou () and Ming Lei ()
Additional contact information
Tianyi Sun: University of Oxford
Alexander Grassam-Rowe: University of Oxford
Zhaoli Pu: Southwest Medical University
Yangpeng Li: Southwest Medical University
Huiying Ren: Southwest Medical University
Yanru An: BGI Research
Xinyu Guo: BGI Research
Wei Hu: The University of Manchester
Ying Liu: Indiana University School of Medicine
Zhu Liu: Southwest Medical University
Kun Kou: Southwest Medical University
Xianhong Ou: Southwest Medical University
Tangting Chen: Southwest Medical University
Xuehui Fan: Southwest Medical University
Yangyang Liu: Indiana University School of Medicine
Shu Tu: University of Oxford
Yu He: University of Oxford
Yue Ren: University of Oxford
Ao Chen: BGI Research
Zhouchun Shang: BGI Research
Zhidao Xia: Swansea University
Lucile Miquerol: Aix Marseille University, CNRS Institut de Biologie du Développement de Marseille UMR 7288
Nicola Smart: University of
Henggui Zhang: The University of Manchester
Xiaoqiu Tan: Southwest Medical University
Weinian Shou: Indiana University School of Medicine
Ming Lei: University of Oxford

Nature Communications, 2023, vol. 14, issue 1, 1-23

Abstract: Abstract The heterogeneity of functional cardiomyocytes arises during heart development, which is essential to the complex and highly coordinated cardiac physiological function. Yet the biological and physiological identities and the origin of the specialized cardiomyocyte populations have not been fully comprehended. Here we report a previously unrecognised population of cardiomyocytes expressing Dbhgene encoding dopamine beta-hydroxylase in murine heart. We determined how these myocytes are distributed across the heart by utilising advanced single-cell and spatial transcriptomic analyses, genetic fate mapping and molecular imaging with computational reconstruction. We demonstrated that they form the key functional components of the cardiac conduction system by using optogenetic electrophysiology and conditional cardiomyocyte Dbh gene deletion models. We revealed their close relationship with sympathetic innervation during cardiac conduction system formation. Our study thus provides new insights into the development and heterogeneity of the mammalian cardiac conduction system by revealing a new cardiomyocyte population with potential catecholaminergic endocrine function.

Date: 2023
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DOI: 10.1038/s41467-023-42658-9

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