A detailed cellular and molecular map of the human heart has been created through a collaboration between several groups of scientists around the globe to improve understanding of its biology in both health and disease.
The team used state-of-the art analysis of large-scale single-cell and nuclei transcriptomes to characterize almost a half million individual cells from six regions of the adult heart. They then used that data to build the most extensive heart cell atlas to date. The atlas shows the huge diversity of cells and cell types. It also predicts how the cells communicate to keep the heart working.
This work helps to set the stage for new therapies and even new types of treatments. “Ultimately, these fundamental insights may suggest specific targets that can lead to individualized therapies in the future, creating personalized medicines for heart disease and improving the effectiveness of treatments for each patient,” said senior study researcher Christine Seidman, M.D., a professor of medicine in the Blavatnik Institute at Harvard Medical School and a cardiovascular geneticist at Brigham and Women’s Hospital.
The research was published in the journal Nature and was led by investigators at Harvard Medical School, Brigham and Women’s Hospital, the Wellcome Sanger Institute, Max Delbrück Center for Molecular Medicine in Germany, Imperial College London and their global collaborators. The research is part of the Human Cell Atlas initiative to map every cell type in the human body.
The team studied nearly 500,000 individual cells and cell nuclei from six different regions of the heart obtained from 14 organ donors whose hearts were healthy, but unsuitable for transplantation. Using a combination of single-cell analysis, machine learning, and imaging techniques, the team could see exactly which genes were switched on and off in each cell.
Their results highlight the cellular heterogeneity of cardiomyocytes, pericytes, and fibroblasts, revealing single distinct atrial and ventricular subsets with diverse developmental origins and specialized properties. They also shed light on the complexity of the cardiac vasculature and its changes along the arterio-venous axis, among other things.
“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,” said Seidman, a co-author on the paper.
The team discovered major differences between cells in regions across the heart. They also observed that each area of the heart had specific subsets of cells, which points to different developmental origins and suggests that these cells would respond differently to treatments.
“This project marks the beginning of new understandings into how the heart is built from single cells, many with different cell states,” noted study co-first author Daniel Reichart, M.D., a research fellow in genetics at Harvard Medical School.
“With knowledge of the regional differences throughout the heart, we can begin to consider the effects of age, exercise and disease and help push the field of cardiology toward the era of precision medicine.”
As part of this study, the researchers also looked at blood vessels running through the heart in unprecedented detail. The data showed how the cells in these veins and arteries are adapted to the different pressures and locations and how this could help researchers understand what goes wrong in blood vessels during coronary heart disease.
The researchers 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 whether any heart cells could be induced to repair themselves. The Heart Cell Atlas will be openly available to researchers worldwide