A cellular and molecular map of the healthy human heart has been created to help clinicians understand what goes wrong in cardiovascular disease.
A global collaboration involving researchers from the Wellcome Sanger Institute, Max Delbrück Centre for Molecular Medicine (MDC), Germany, Harvard Medical School, and Imperial College London analysed almost half a million individual cells to build a first extensive draft cell atlas of the human heart.
It is published in the latest edition of Nature and reveals the diversity of cells, heart muscle cell types, cardiac protective immune cells, and the intricate network of blood vessels. It also predicts how the cells communicate to keep the heart working.
Undertaken as part of the Human Cell Atlas initiative to map every cell type in the human body, the heart atlas will also guide more personalised medicine and could eventually lead to regenerative medicine, say the research team.
Researchers studied nearly 500,000 individual cells and cell nuclei from six different regions of healthy hearts from 14 organ donors. Using single cell technology, machine learning and imaging techniques, the team was able to establish which genes were switched on in each cell.
They discovered major differences in the cells in different areas of the heart, and that each area of the heart had specific sets of cells, which highlighted different developmental origins and potentially different responses to treatments.
The six areas of the heart contained 11 different cell types and the team discovered more than 62 different cell states, which had never been seen before in this detail.
First author Dr Carlos Talavera-López from the Wellcome Sanger 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.”
Senior author Professor Norbert Hübner, of the Max Delbrück Centre for Molecular Medicine, Charité – Universitätsmedizin Berlin, the Berlin Institute of Health and Deutsches Zentrum für Herz-Kreislauf-Forschung, Germany, said: “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.
“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 a fundamental necessity to understand how the heart functions and start to unravel how it responds to stress and disease.”
As part of the study, the research team also examined the blood vessels running through the heart in unprecedented detail, showing how he cells in these veins and arteries are adapted to the different pressures and locations, which could help understand what goes wrong in the blood vessels during coronary heart disease.
They also focused on understanding cardiac repair, looking at how the immune cells interact and communicate with other cells in the healthy heart, and how this differs from skeletal muscle. Further research will include investigating if any heart cells could be induced to repair themselves.
Litvinuková M, Talavera-López C, Maatz H et al. Cells of the adult human heart. Nature 23 September 2020; doi: 10.1038/s41586-020-2797-4
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