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Better understanding the heart cell by cell: Atlas of the human heart published

Zooming in very closely: With the help of single cell sequencing, scientists have examined the cellular and molecular details of heart cells. For the first time, the Human Heart Cell Atlas is the first comprehensive work on heart cell types, subtypes and blood vessel cells. | ©Design Cells - stock.adobe.com

Prof. Norbert Hübner is Principle Investigator at the DZHK and one of the main authors of the study. | ©MDC

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An international team of researchers from six countries has analysed around half a million individual cells and cell nuclei of the human heart. The scientists want to understand how the healthy heart "ticks" and what goes wrong in heart disease. This should enable new treatments and finding ways of regenerating damaged heart tissue. In a first detailed draft of the Human Heart Cell Atlas, published in Nature, the researchers show the huge diversity of cells and molecules.

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"This is the first time anyone has looked at the single cells of the human heart at this scale, which has only become possible with large-scale single cell sequencing," says Professor Norbert Hübner, Principal Investigator at the DZHK and one of the main authors from the Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC), Charité – Universitätsmedizin Berlin and the Berlin Institute of Health (BIH). "This study shows the power of single cell genomics and international collaboration. Knowledge of the full range of cardiac cells and their gene activity is fundamental to understanding how the heart functions and to unravel how it responds to stress and disease."

Until now, amazingly little is known about how precisely the cells in each part of the heart coordinate with each other for every heartbeat, ensuring that the body is constantly supplied with nutrients and oxygen through the blood and that waste products and carbon dioxide are carried away. For their work, the researchers used seven female and seven male hearts from brain-dead donors between 40 and 75 years of age whose hearts were healthy but not suitable for transplantation. To characterise the heart cells as precisely as possible, the team investigated which genes are switched on in the individual cells and cell nuclei from six different heart regions.

In addition to the enormous cell diversity, the atlas reveals previously unknown subtypes of heart muscle cells and supporting cardiac cells, protective immune cells in the heart, and an intricate network of blood vessel cells. It also predicts how the cells communicate to keep the heart working.

A better understanding of the healthy heart and the abnormalities in a diseased heart could improve the availability of individualized therapies. For example, the researchers found that the cells in different parts of the heart differ widely. This might lead to different responses to treatment. The researchers also studied the blood vessels running through the heart in more detail than ever before. The atlas shows how the cells in these veins and arteries are adapted to different pressures and locations. This could help understand what goes wrong in the blood vessels during coronary heart disease.

The Huma Heart Cell Atlas is part of the international project "Human Cell Atlas". 33 scientists from 19 institutions in Germany, the United Kingdom, the United States, Canada, China, and Japan are involved. It is funded by the Chan Zuckerberg Initiative with almost four million US dollars as well as by the German Centre for Cardiovascular Research (DZHK) and the British Heart Foundation (BHF) with 2.5 million euros. It was established around three years ago by a research group led by Prof. Hübner together with Dr. Sarah Teichmann from Wellcome Sanger Institute in Cambridge, UK, Prof. Jonathan Seidmann and Prof. Christine Seidmann, both from Harvard Medical School in Boston, and Dr. Michela Noseda from Imperial College London. The DZHK scientists Dr. Henrike Maatz from the working group of Norbert Hübner and Dr. Daniel Reichart from the University Medical Center Hamburg-Eppendorf belong to the four first authors of the study.

The Heart Cell Atlas is openly available to researchers worldwide. All data of the study can be explored online.

The publication is Paper of the Month | October 2020 of the DZHK.

Original publication: Monika Litviňuková, Carlos Talavera-López, Henrike Maatz, Daniel Reichart et al. (2020): "Cells of the adult human heart". Nature, DOI: 10.1038/s41586-020-2797-4

Scientific contacts:
Prof. Norbert Hübner, Head of the Genetics and Genomics of Cardiovascular Disease Group, Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC), nhuebner(at)mdc-berlin.de

Dr. Henrike Maatz, Postdoc researcher in the Genetics and Genomics of Cardiovascular Disease Grouply, Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC), h.maatz(at)mdc-berlin.de

Source: Press release Max Delbrück Centre for Molecular Medicine in the Helmholtz Association