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Sanger Institute scientists help map the human heart in unprecedented detail

Scientists have created the most detailed map of the human heart to date, which will improve our understanding of cardiovascular disease.

Researchers at the Wellcome Sanger Institute and their collaborators created the cellular and molecular map to aid our knowledge of how the organ works and pave the way for more personalised medicine.

Understanding the human heart at a cellular level can aid our understanding of disease
Understanding the human heart at a cellular level can aid our understanding of disease

They studied nearly 500,000 individual cells and cell nuclei from six different regions of healthy hearts from 14 organ donors.

Single cell technology, machine learning and imaging techniques enabled the team to see exactly which genes were switched on in each cell.

The resulting atlas captures the huge diversity of cells and reveals heart muscle cell types, cardiac protective immune cells and the intricate network of blood vessels, and predicts how the cells communicate to keep the heart working.

Dr Carlos Talavera-López, one of the first authors from the Wellcome Sanger Institute , and previously at the EMBL European Bioinformatics Institute, said: “For the first time, we could see exactly what each cell is doing in the human heart. This atlas shows that the cells in each of the four chambers of the heart behave differently to each other, mirroring the different functions of each area and helping us understand the healthy human heart.”

They found 11 different cell types across the six areas of the heart and discovered more than 62 different cell states – something never seen before in such detail.

Our hearts beat 100,000 times a day, with a one-way flow through four chambers, varying in speed with rest, exercise and stress. This extremely complex mechanism requires cells in each part of the heart to coordinate with each other for every heartbeat.

Studying the blood vessels running through the heart in unprecedented detail, the researchers showed cells in these veins and arteries are adapted to the different pressures and locations. This could shed light on what goes wrong in the blood vessels during coronary heart disease.

Dr Sarah Teichmann with the computer cluster at the Sanger Institute. Picture: Pari Naderi
Dr Sarah Teichmann with the computer cluster at the Sanger Institute. Picture: Pari Naderi

Some 17.9 million die from cardiovascular disease worldwide each year, making it the leading cause of death, with heart attacks and strokes responsible for the majority of these.

The study, also involving Max Delbrück Center for Molecular Medicine (MDC) in Germany, Harvard Medical School, Imperial College London and other global collaborators, was published in Nature.

Prof Christine Seidman, a senior author from Brigham and Women’s Hospital, Harvard Medical School and Howard Hughes Medical Institute, said: “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 individualised therapies in the future, creating personalised medicines for heart disease and improving the effectiveness of treatments for each patient.”

The researchers also explored cardiac repair by examining how the immune cells interact and communicate with other cells in the healthy heart, and how this differs from skeletal muscle. Further research will investigate whether any heart cells could be induced to repair themselves, which could lead to advances in regenerative medicine.

Dr Michela Noseda, a senior author from the National Heart and Lung Institute, Imperial College London, said: “We mapped the cardiac cells that can be potentially infected by SARS-CoV-2 and found that specialised cells of the small blood vessels are also virus targets. Our datasets are a goldmine of information to understand subtleties of heart disease.”

Dr Sarah Teichmann , a senior author from the Wellcome Sanger Institute and co-chair of the Human Cell Atlas Organising Committee, said: “This great collaborative effort is part of the global Human Cell Atlas initiative to create a ‘Google-map’ of the human body. Openly available to researchers worldwide, the Heart Cell Atlas is a fantastic resource, which will lead to new understanding of heart health and disease, new treatments and potentially even finding ways of regenerating damaged heart tissue.”

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