Dandan L, Jinfeng X, Li G, Liping Z, Bo L, Qiao Z, Ke X, Huixing Z, Duanyang X, Fulei Z, Jie L, Yi L, Li L, Jian Y, Zhigang X, Yi-Han C
Nature Communications 2021
The sinoatrial node (SAN) is a small collection of specialized muscle fibers, located in the right atrium of the heart. The SAN generates bioelectrical impulses that are responsible for the contraction of the heart in mammals. In this study, the authors investigated the underlying molecular and cellular components crucial to the function of the SAN. Specific genes in human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) were altered to analyze the role of distinct cell clusters in SAN and changes in cardiac beat rate was recorded in a multiwell microelectrode array (MEA) system. Of the four distinct transcriptional clusters identified by single-cell RNA sequencing to be important to SAN fucntion, deficiency in one of the genes, Vsnl1, was found to play a large role in the reduction of beat rate in human iPSC-CMs. Data from the MEA system showed a reduction in hiPSC-CM beat rate by 44.8% of the control. Furthermore, results from the in vitro experiment collected with the MEA system matched in vivo data where Vsnl1-deficient mice hearts also displayed reduced heart rate. Overall, this study presents findings that improve understanding of SAN function in the heart.