Tools to Understand Heart Contraction
By Amanda Chase
November 25, 2019
The heart enables blood to be pumped throughout the body. This is done through a series of coordinated signaling that stimulates muscle contractions, and is coordinated by the cardiac conduction system. The cardiac conduction system (CCS) is made up of a group of specialized cardiac muscle cells that each carry out a particular task to establish the coordinated contractions and the rhythmic beating of the heart. The CCS is essential for normal function of the heart. Dysfunction in the CCS causes irregular, fast, or slow heart rhythms, and severe cases can result in arrhythmias, decreased cardiac output, or sudden death.
The CCS is composed of several unique cardiac cells, each with their own physiological and electrochemical properties. However, there is currently limited knowledge on the distinct CCS cell types, which would allow a better understanding of the cellular and molecular landscape that facilitates heart development and function. Recently, a group of researchers with the Stanford Cardiovascular Institute, led by William Goodyer, MD, PhD, and senior author Sean Wu, MD, PhD, addressed this gap in knowledge by leveraging single-cell RNA sequencing to understand global gene expression analysis at a single-cell resolution. The work was recently published in Circulation Research.
Single-cell RNA sequencing (scRNA-seq) provides a higher resolution of cellular differences to provide a better understanding of the function of an individual cell. In this paper, the authors performed scRNA-seq on over twenty thousand cells from heart tissues enriched for CCS cells in the developing mouse hearts to successfully capture all components of the CCS, including cell types that were previously unattainable. They were also able to discover a unique set of genes expressed in the CCS, as well as various cell subtypes, and were able to uncover several novel markers and unique molecular signatures of various cell subtypes to provide a molecular blueprint of the CCS. This study provided the first look at the entire CCS at the single-cell level, which has important implications for understanding CCS role in heart development and function. Furthermore, the authors provide a tool to facilitate future efforts to isolate and characterize cells in the context of development and disease. Together, the information and tools derived from this work will improve our ability to diagnose and treat diseases of the CCS (i.e., arrhythmias) in utero and during adulthood.
Other authors from the Stanford Cardiovascular Institute include Benjamin Beyersdorf, David Paik, Lei Tian, Guang Li, Jan Buikema, Orlando Chirikian, Sneha Venkatraman, and Joseph Wu. Other Stanford authors include Marc Tessier-Lavigne, Shannon Choi, and Eliza Adams. Funding was provided by the NIH Office of Director’s Pioneer Award LM012179-03; the AHA Established Investigator Award 17EIA33410923; NIH R01 HL141371, R01 HL145676, R01 130020, EB009035, and T32 HL094274; and a Stanford BioX Bowes Fellowship.