Dr Michela Noseda from the National Heart and Lung Institute is part of an international collaboration aiming to better understand heart failure.

Scientists have created a cellular and molecular map of the healthy human heart, to understand how this vital organ functions, and to shed light on what goes wrong in cardiovascular disease. Researchers from Imperial College London, the Wellcome Sanger Institute, Max Delbrück Center for Molecular Medicine (MDC), Harvard Medical School and their global collaborators analysed almost half a million individual cells to build a first extensive draft cell atlas of the human heart. The atlas reveals the huge diversity of cells including heart muscle cell types, cardiac protective immune cells, and cells of the intricate network of blood vessels. It also predicts how the cells communicate to keep the heart working.

"Our datasets are a goldmine of information to understand subtleties of heart disease" Dr Michela Noseda

Published today in Nature (September 2020), this study is part of the Human Cell Atlas initiative to map every cell type in the human body. The new molecular and cellular knowledge of the heart will enable better understanding of heart disease and guide more personalised medicine. In this new study, researchers studied nearly 500,000 individual cells and cell nuclei from six different regions of healthy hearts from 14 organ donors. Using cutting edge, single cell technology, machine learning and imaging techniques, the team could see exactly which genes were switched on in each cell.

Unexpected findings

The six areas of the heart contained 11 different cell types and the researchers discovered more than 62 different cell subtypes, which had never been seen before in this detail. The researchers discovered that there were major differences in the cells in different areas of the heart, and that each area of the heart had specific sets of cells, highlighting different developmental origins and potentially different responses to treatments. One unexpected finding was that the ventricles of the female hearts had higher numbers of muscle cells and fewer connective tissue cells than those of the male hearts – even though they are typically smaller. This finding may be a hint why women are less vulnerable than men to cardiovascular diseases. “It’s intriguing but it’s based on just seven hearts of each gender. We’ll have to see whether this result holds up to further investigation,“ says MDC researcher Dr Henrike Maatz.

Tackling the number one killer

Cardiovascular disease is the leading cause of death worldwide, killing an estimated 17.9 million people each year, with heart attacks and strokes causing the majority of these. To understand what happens during heart disease and create better therapeutic strategies, it is vital to know the intricate molecular processes in the cells of the healthy heart. As part of this study, the researchers studied the blood vessels running through the heart in unprecedented detail. The atlas showed how the cells in these capillaries, veins and arteries are adapted to the different pressures and locations, and could help understand what goes wrong in the blood vessels during myocardial infarction and other diseases of the cardiac muscle.

Dr Michela Noseda said: “Our international effort provides an invaluable set of information to the scientific community by illuminating the cellular and molecular details of cardiac cells that work together to pump blood around the body. We used data from the heart cell atlas to map the cardiac cells that can be potentially infected by SARS-CoV-2 and found that specialized cells of the small blood vessels are also virus targets. Our datasets are a goldmine of information to understand subtleties of heart disease and how our precious heart works”.  

Getting to the heart of the matter

All known cell types in the heart also contain numerous subtypes. There is, for instance, not one heart muscle cell, but many different cardiomyocytes with, in some cases, different functions. The gene expression profiles indicate that of some of them are equipped to handle a much higher metabolic rate than others. The researchers don’t yet know why this is so. They also found very different patterns of gene expression in the fibroblasts that form the heart’s connective tissue.

Professor Christine Seidman from Brigham and Women’s Hospital, Harvard Medical School and Howard Hughes Medical Institute, said: “Millions of people are undergoing treatments for cardiovascular diseases. Understanding the healthy heart will help us understand interactions between cell types and cell states that can allow lifelong function and how these differ in diseases. Ultimately these fundamental insights may suggest specific targets that can lead to individual therapies in the future, creating personalised medicines for heart disease, and improving the effectiveness of treatments for each patient.”

Read the full publication in Nature 'Cells of the adult human heart'