A new study, published today in the journal Nature, has unveiled the most comprehensive and detailed Human Heart Cell Atlas to date. The atlas includes the specialized tissue of the cardiac conduction system, which is responsible for initiating the heartbeat.
Led by the Wellcome Sanger Institute and the National Heart and Lung Institute at Imperial College London, a team of researchers has developed this atlas as part of the international Human Cell Atlas (HCA) initiative. The HCA aims to map every cell type in the human body to enhance our understanding of health and disease. The newly created Human Heart Cell Atlas will serve as a foundation for the integrated HCA Human Heart Cell Atlas.
The study describes 75 distinct cell states across eight regions of the human heart, offering unprecedented insight into the cells of the cardiac conduction system. This system acts as the heart’s electrical wiring, transmitting electrical signals from the top to the bottom of the heart, ensuring coordinated heartbeats.
Using spatial transcriptomics, a technique that reveals the location of cells within tissues, researchers have also deciphered the communication patterns between these cells for the first time. This molecular guidebook showcases the characteristics of healthy cells, providing a valuable reference to better understand disease mechanisms, particularly those affecting heart rhythm.
Establishing a Human Heart Cell Atlas is of utmost importance, as cardiovascular diseases remain the leading cause of global mortality. In the UK alone, around 20,000 electronic pacemakers are implanted each year to treat these conditions. However, these devices can be ineffective and prone to complications and side effects. By comprehending the biology of the conduction system cells and differentiating them from muscle cells, new avenues for therapies to enhance cardiac health and develop targeted treatments for arrhythmias can be explored.
The research team also introduces a novel computational tool named Drug2cell, which offers insights into the effects of drugs on heart rate. Leveraging single-cell profiles and a vast database of 19 million drug-target interactions, Drug2cell can predict drug targets as well as potential side effects. Surprisingly, the tool identified that certain medications, such as GLP1 drugs used for diabetes and weight loss, target pacemaker cells, potentially explaining their side effect of increased heart rate. The team confirmed this finding using an experimental stem cell model of pacemaker cells.
Dr. James Cranley, a cardiologist specializing in heart rhythm disorders and a PhD student at the Wellcome Sanger Institute, expressed the significance of this study, stating that it sheds light on poorly understood cells of the cardiac conduction system. This newfound understanding opens doors to targeted anti-arrhythmic therapies in the future.
Furthermore, the study made an unexpected discovery by revealing a close relationship between glial cells, traditionally found in the brain, and conduction system cells. Glial cells, part of the nervous system, seem to physically interact with conduction system cells, potentially playing a supportive role by facilitating communication with pacemaker cells, guiding nerve endings, and supporting the release of the neurotransmitter glutamate.
Another important finding from the study is the identification of an immune structure on the heart’s outer surface containing plasma cells. These cells release antibodies into the surrounding space, protecting the heart from infections originating in the nearby lungs. Additionally, the researchers discovered a cellular niche associated with a hormone that could serve as an early indicator of heart failure.
Dr. Michela Noseda, a coordinator of the Human Cell Atlas Heart BioNetwork and senior lecturer in Cardiac Molecular Pathology at the National Heart and Lung Institute, Imperial College London, emphasized the significance of the Drug2cell platform in evaluating new treatments and their potential effects on the heart’s electrical impulses.
“We often don’t fully know what impact a new treatment will have on the heart and its electrical impulses – this can mean a drug is withdrawn or fails to make it to the market,” Dr. Michela Noseda added.
“Our team developed the Drug2cell platform to improve how we evaluate new treatments and how they can affect our hearts, and potentially other tissues too. This could provide us with an invaluable tool to identify new drugs which target specific cells, as well as help to predict any potential side-effects early on in drug development.”
Professor Metin Avkiran, Associate Medical Director at the British Heart Foundation, highlighted the impact of this research in advancing our understanding of specialized regions within the human heart and their intercellular communication.
“The new findings on the heart’s electrical conduction system and its regulation are likely to open up new approaches to preventing and treating rhythm disturbances that can impair the heart’s function and may even become life-threatening.”
Dr. Sarah Teichmann, a senior author of the study, described the Heart Cell Atlas as a valuable resource that provides “cardiac microanatomy in unprecedented detail, including the cardiac conduction system that enables each heartbeat, and is a valuable reference for studying heart disease and designing potential therapeutics.”
Overall, this groundbreaking study offers a comprehensive and detailed understanding of human heart cells, including the specialized cardiac conduction system. It provides a crucial foundation for further research and the development of targeted therapies for heart-related disorders, ultimately benefiting patients worldwide.
Source: 10.1038/s41586-023-06311-1
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