Scientists mapped out the beat of our heart, here's what they found

Like the brain, our heart also has an intricate network of cells that makes it work, known as the cardiac conduction system (CCS). Here are some secrets the CCS holds within.
Rupendra Brahambhatt
The human heart
The human heart

Rasi Bhadramani/iStock  

Researchers from the Wellcome Sanger Institute and the Imperial College of London have successfully mapped the cells in the heart’s cardiac conduction system (CCS). 

In their recently published study, they have also proposed a tool called Drug2cell that can predict the effect of any new drug treatment on the human heart. 

CCS is a complex network of muscles, nodes, and signals in our heart’s walls that makes our heart beat. The researchers not only profiled CCS but a total of 75 cell types in eight regions of the heart. 

“The cardiac conduction system is critical for the regular and coordinated beating of our hearts, yet the cells which make it up are poorly understood,” said Dr. James Cranley, co-lead researcher and a Ph.D. Fellow at Sanger.

They claim that it’s the first time such a detailed mapping of human heart cells has been achieved. The information from their study can drastically improve our understanding of the heart.

“This study sheds new light by defining the profiles of these (CCS) cells, as well as the multicellular niches they inhabit. This deeper understanding opens the door to better, targeted anti-arrhythmic therapies in the future,” he added.

What does the heart map reveal?

Scientists mapped out the beat of our heart, here's what they found
Multimodal profile of the human heart.

The current study is part of the Human Cell Atlas (HCA) program, a global research initiative that aims to fully map the 37.2 trillion cells that make up the human body. Over 2,900 scientists in 94 countries are working on this ambitious project. 

There are various methods to profile cells that form the different organs in our body. One such method is spatial transcriptomics which allows scientists to examine the RNA strands inside the genome of a cell. 

Dr. Cranley and his team studied healthy and diseased heart cells and mapped the differences in their respective RNA transcripts. These differences highlight the molecular changes that take place during the time a healthy cell turns into a diseased one.   

Here are some of the key findings revealed by the researchers:

  • Glial cells, also found in the brain, have received limited attention in the heart. The study uncovers their physical interaction with CCS cells, suggesting a vital supportive role. Specifically, glial cells appear to communicate with pacemaker cells, guide nerve endings to them, and assist in releasing the neurotransmitter glutamate that changes the heart rate and cardiac output.

  • Some muscle cells in a diseased heart produce Brain Natriuretic Peptide (BNP), a hormone that serves as a clinical biomarker for detecting heart failure. The researchers discovered that even healthy heart cells also produce some amount of BNP, and the number of such cells increases as the heart becomes more prone to failure. 

  • The immune system is designed to protect the human heart from both internal and external threats. For instance, plasma cells located right outside our heart’s surface release antibodies to protect the heart from infections affecting nearby organs such as the lungs. 

“Using cutting-edge technologies, this research provides further intricate detail about the cells that make up specialized regions of the human heart and how those cells communicate with each other,” said Metin Avkiran, the director of the British Heart Foundation and an expert in molecular cardiology.

“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,” he added.

Significance of the drug2cell tool

The European Bioinformatics Institute maintains a “manually curated database” (known as the ChEMBL database) containing information related to millions of bioactive molecules demonstrating drug-like behavior. 

The researchers utilized this information to create their drug2cell tool that draws upon the extensive database of 19 million drug-target interactions found in EBI’s ChEMBL database. It can forecast which cells a new drug is likely to target and what could be its side effects.

Certain drugs that are used for weight loss or to treat diabetes make the heart beat faster. Even scientists do not know why this happens, but thanks to the drugs2cell tool, the researchers were able to predict the expression of pacemaker cells against such drugs.

“The mechanism of activating and suppressing pacemaker cell genes is not clear, especially in humans. This is important for improving cell therapy to facilitate the production of pacemaker cells or to prevent the excessive spontaneous firing of cells. By understanding these cells at an individual genetic level, we can potentially develop new ways to improve heart treatments,” said Dr. Kazumasa Kanemaru, co-lead study author and a postdoc at Sanger. 

The study is published in the journal Nature.

Study Abstract:

The function of a cell is defined by its intrinsic characteristics and its niche: the tissue microenvironment in which it dwells. Here we combine single-cell and spatial transcriptomics data to discover cellular niches within eight regions of the human heart. We map cells to microanatomical locations and integrate knowledge-based and unsupervised structural annotations. We also profile the cells of the human cardiac conduction system. The results revealed their distinctive repertoire of ion channels, G-protein-coupled receptors (GPCRs) and regulatory networks, and implicated FOXP2 in the pacemaker phenotype. We show that the sinoatrial node is compartmentalized, with a core of pacemaker cells, fibroblasts and glial cells supporting glutamatergic signalling. Using a custom module, we identify trans-synaptic pacemaker cell interactions with glia. We introduce a druggable target prediction tool, drug2cell, which leverages single-cell profiles and drug–target interactions to provide mechanistic insights into the chronotropic effects of drugs, including GLP-1 analogues. In the epicardium, we show enrichment of both IgG+ and IgA+ plasma cells forming immune niches that may contribute to infection defence. Overall, we provide new clarity to cardiac electro-anatomy and immunology, and our suite of computational approaches can be applied to other tissues and organs.

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