Cardiovascular diseases are the leading cause of death worldwide. But some people face a higher risk than others – for example, African-Americans in the US are affected much more often than Hispanics. In addition to socioeconomic disparities, genetic determinants also apparently influence how such diseases progress and how effective the treatments are.
But what exactly links the unequal risks? To answer this question, the Human Heart Cell Atlas – coordinated by Jonathan Seidman, Bugher Professor of Cardiovascular Genetics at Harvard Medical School, and Professor Norbert Hübner from the Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC) – will additionally characterize the cellular and molecular signatures of healthy hearts from African-American and Hispanic donors. The project is also collaborating with partners in Brazil and Canada, such as Professor Gavin Oudit from the Mazankowski Alberta Heart Institute at the University of Alberta.
“African-Americans have, for example, lower rates of atherosclerosis but higher rates of coronary artery disease than white Americans. They also have higher rates of hypertension but lower rates of atrial fibrillation,” says Seidman. “We hypothesize that there are differences in the interaction between cell types and cell states, causing the heart to respond differently to normal biological processes and diseases, not just in African Americans but in peoples with many different ancestries.”
It all begins with a healthy organ
The scientists want to analyze the full spectrum of the heart cells and their gene activity and then compare these findings with the existing data on Europeans. “Our starting point here is also the healthy heart,” says Norbert Hübner from the MDC, Charité – Universitätsmedizin Berlin, the Berlin Institute of Health (BIH ) and the German Centre for Cardiovascular Research (DZHK ). Hübner, along with Dr. Sarah Teichmann from the Wellcome Sanger Institute in Cambridge, UK; Jonathan Seidman und Christine Seidman, both from Harvard Medical School in Boston; and Dr. Michela Noseda from Imperial College London; launched the Heart Cell Atlas about three years ago to gain a better understanding of the heart, cell by cell.
The Heart Cell Atlas is part of the global Human Cell Atlas initiative, which is run by a collaborative community of world-leading scientists. The Chan Zuckerberg Initiative (CZI) is supporting the project under its CZI Seed Networks for the Human Cell Atlas. To make the diversity research possible, the US philanthropic organization will provide additional funding. CZI is supporting diversity projects on various tissues and organs by ten such Seed Networks, as it announced on October 28, 2020.
"It is critical to include diverse tissue samples in the Human Cell Atlas so we can learn and grow from historical shortcomings and bias in genomics,” says Norbert Tavares, CZI Program Manager for Single-Cell Biology. “While this effort is only the start of addressing diversity in the HCA in the long term, these projects will serve as an initial pilot to surface future opportunities to more deeply address these challenges for the future.”
Scientific contact: 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