A team of scientists created the first cardiac cell atlas. It provides a new basis for studying heart disease and developing therapies.
Although we hardly notice it most of the time, the constant beating of a human heart is an incredibly complex task. Like an orchestra, thousands of cells have to master their individual performances and work together.
Now, a team of scientists created the first human heart cell atlas, a collection of maps showing almost half a million heart cells and identifies the role of each in the symphony of the heart. In the work published today in the magazine Nature, the researchers examined six regions in 14 healthy donor hearts, creating a detailed database that provides a new basis for comparison to study heart disease, the leading cause of death worldwide.
To understand what is wrong with various cardiovascular conditions, “we must first know what is normal,” says Christine Seidman, Howard Hughes Medical Institute researcher, Harvard University cardiovascular geneticist and director of the Center for Cardiovascular Genetics at Brigham Hospital. and Women’s.
“Monumental”This is how cardiologist Douglas Mann, from the Washington University School of Medicine in St. Louis, defined the work, who was not involved in the study. “I think it is a great achievement and it will be a great reference source for the field”.
The importance of the atlas is that cardiac cells are particularly difficult to study. Unlike some cancer cells and other tissues, those of the heart cannot be grown indefinitely in the laboratory for analysis. For this reason, much of the cardiac research is carried out with mice, whose hearts differ significantly from those of humans.
On the other hand, healthy human hearts can be difficult to find (most are used in transplants). Seidman’s team built on those unusual cases in which healthy hearts were rejected for transplantation and could be frozen for research use. First, the researchers used a high-throughput sequencing method to define the individual characteristics of each heart cell. They then mapped those cells into six regions of 14 human hearts, seven from men and seven from women. “For the first time, we have a Postal Code for each cell to find out which population it belongs to, “says Seidman.
The team also analyzed the RNA levels of heart cells using fluorescent markers to obtain molecular details of its function. Identifying not just where the cells are, but what proteins they make will be a great help to research, says Mann. For example, by comparing cells from diseased hearts to those from healthy hearts using the atlas, researchers could identify differences and point to new therapies for heart disease.
Although the researchers studied a relatively small group of hearts (“14 people cannot replicate the world population”, Seidman says), the new atlas revealed some biological surprises. The team found previously unknown cellular diversity in various parts of the heart. They also discovered differences between the healthy hearts of men and women; women had a higher proportion of heart muscle cells, called cardiomyocytes, than men. More research is needed on that topic, Seidman says, as those cells could hold clues to differences in heart disease between the sexes.
Beyond that, “what we see is a surprising heterogeneity, in terms of the various types of cells that we now know make up human heart tissue and in terms of regional differences within the heart, “says cardiologist Hugh Watkins of the University of Oxford in England, who was also not part of the study team “It certainly is a much more complicated organ than many might have imagined,” he said.
The atlas is part of the Human Cell Atlas initiative, an effort funded by the Chan Zuckerberg Initiative to map all cell types in the human body. “It takes a big village to do this,” Seidman noted. To create the heart atlas, his group worked with an international interdisciplinary team of experts, from cardiac surgery to computational biology.
In the future, the researcher and her team plan to expand the atlas to a more diverse population (the initial hearts were all from white donors). And they are also beginning to compare the proteins produced in healthy heart cells with those affected by heart disease.
“In due course, what we really want to know is how the different cell types fit together at the microscopic and functional level,” says Watkins. “That is another ambitious goal, but the atlas provided here is an exciting start“.