A multinational team of scientists led by Harvard Medical School, Brigham and Women’s Hospital, the Wellcome Sanger Institute, Max Delbrück Center for Molecular Medicine and Imperial College London has created a detailed cellular and molecular map of six anatomical adult heart regions.
“To understand what’s going wrong in various forms of heart disease, first we need to know what is normal,” said Dr. Christine Seidman, a cardiovascular geneticist at Harvard University and Howard Hughes Medical Institute, and director of the Cardiovascular Genetics Center at Brigham and Women’s Hospital.
“I can summarize my thoughts in one word: monumental,” added Dr. Douglas Mann, a cardiologist at Washington University School of Medicine.
“I think it’s a really big accomplishment and will be a tremendous source of reference for the field.”
The researchers used a high-throughput sequencing method to define individual characteristics of every heart cell.
They then mapped those cells in six regions of 14 healthy donor hearts, seven from men and seven from women.
They also analyzed RNA levels of heart cells using fluorescent markers to glean molecular details of their function.
“Identifying not only where cells are, but which proteins they’re producing, will be a particular boon for research,” Dr. Mann said.
For instance, by comparing cells in diseased hearts to those in healthy hearts using the atlas, researchers might pinpoint differences and target new therapies for heart disease.
Though the team studied a relatively small group of hearts, the new atlas revealed some biological surprises.
The six areas of the heart contained 11 different cell types and the authors discovered more than 62 different cell subtypes, which had never been seen before in this detail.
They also uncovered differences between the healthy hearts of males and females; females had a greater proportion of heart muscle cells, called cardiomyocytes, than males.
“That warrants more research as those cells might hold clues to differences in heart disease between the sexes,” Dr. Seidman said.
“Now we have a single-cell atlas of the normal human heart, including cellular composition and gene expression,” said Professor Gavin Oudit, a researcher at the University of Alberta.
“This is the first step toward understanding heart disease and developing new targeted treatments to stop it.”
“What we are working on now is to see how the cell types and gene expression are changed in patients with genetic cardiomyopathies.”
“Our international effort provides an invaluable set of information to the scientific community by illuminating the cellular and molecular details of cardiac cells that work together to pump blood around the body,” said Dr. Michela Noseda, a researcher at the National Heart and Lung Institute and the British Heart Foundation Centre of Research Excellence and Centre of Regenerative Medicine at Imperial College London.
“We used data from the heart cell atlas to map the cardiac cells that can be potentially infected by SARS-CoV-2 and found that specialized cells of the small blood vessels are also virus targets.”
“Our datasets are a goldmine of information to understand subtleties of heart disease and how our precious heart works.”
“This project marks the beginning of new understandings into how the heart is built from single cells, many with different cell states,” said Dr. Daniel Reichart, a geneticist 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.”
“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,” said Professor Norbert Hübner, a researcher at Max Delbrück Center for Molecular Medicine.
“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 to start to unravel how it responds to stress and disease.”
The new atlas is part of the Human Cell Atlas initiative, an effort funded by the Chan Zuckerberg Initiative to map all the cell types in the human body.
“In due course, what we really want to know is how the different cell types fit together at the microscopic and functional level,” Dr. Watkins said.
“That’s another ambitious goal, but the atlas provided here is an exciting start.”
The team’s paper was published online today in the journal Nature.
M. Litviňuková et al. Cells of the adult human heart. Nature, published online September 24, 2020; doi: 10.1038/s41586-020-2797-4