Normal cardiac automaticity is dependent on the pacemaker cells of the sinoatrial node (SAN). Insufficient cardiac pacemaking leads to the development of sick sinus syndrome (SSS). Since currently available pharmaceutical drugs and implantable pacemakers are only partially effective in managing SSS, there is a critical need for developing targeted mechanism-based therapies to treat SSS. SAN-like pacemaker cells (SANLPCs) are difficult to regenerate in vivo or in vitro because the genes and signaling pathways that regulate SAN development and function have not been fully elucidated. The development of more effective treatments for SSS, including biological pacemakers, requires further understanding of these genes and signaling pathways. Compared with genetic models and bulk RNA sequencing, single-cell RNA sequencing (scRNA-seq) technology promises to advance our understanding of cellular phenotype heterogeneity and molecular regulation during SAN development. This review outlines the key transcriptional networks that control the structure, development, and function of the SAN, with particular attention to SAN markers and signaling pathways detected via scRNA-seq. This review offers insights into the process and transcriptional network of SAN morphogenesis at a single-cell level and discusses current challenges and potential future directions for generating SANLPCs for biological pacemakers.

A 44‑year‑old male patient was referred to our department with unremarkable physical examination and laboratory data due to a mass which was incidentally found in the right atrial during a routine examination.Transthoracic and transesophageal echocardiography revealed a 46×30 mm, well-delimited, non-mobile mass in the superior portion of the right atrium. Besides the intracardiac mass, another low density was detected in adjacent pericardial cavity at cardiac computed tomography ;he extracardiac mass appeared to be caused by invasive growth from the intracardiac mass.An operation was performed through right anterolateral minithoracotomy with the patient under hypothermic cardiopulmonary bypass. During operation, it was found that the surface of the right atrium was covered by an adipose mass (30×40 mm; Fig. 2A). Intracardiac mass also showed yellow adipose tissue (40×50 mm; Fig. 2B). Both parts of the mass infiltrated the myocardium. The mass was resected completely; and right atrium was reconstructed by using bovine pericardium pad. After the operation, the pathology confirmed the both intracardiac and extracardiac tissues as lipoma; transthoracic echocardiogram showed the atrial mass was removed completely and the left ventricular ejection fraction was normal . The patient’s postoperative course was uneventful and he was discharged home after 7 days.

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