By Lisa Kadyk, PhD. CIRM Senior Science Officer
I love maps; I still have auto club maps of various parts of the country in my car. But, to tell the truth, those maps just don’t have as much information as I can get by typing in an address on my cell phone. Technological advances in global positioning systems, cellular service, data gathering and storage, etc. have made my beloved paper maps a bit of a relic.
Similarly, technological advances have enabled scientists to begin making maps of human tissues and organs at a level of detail that was previously unimaginable. Hundreds of thousands of single cells can be profiled in parallel, examining expression of RNA and proteins. These data, in combination with new three-dimensional spatial analysis techniques and sophisticated computational algorithms, allow high resolution mapping of all the cells in a given tissue or organ.
Given these new capabilities, an international “Human Cell Atlas Consortium” published a white paper in 2017 outlining plans and strategies to build comprehensive reference maps of all human cells, organ by organ. The intent of building such an atlas is to give a much better understanding of the biology and physiology of normal human tissues, as well as to give new insights into the nature of diseases affecting those tissues and to point the way to developing new therapies.
One example of this new breed of cartography was published September 24 in the journal Nature, in a paper called simply “Cells of the Human Heart”. This tour-de-force effort was led by scientists from Harvard Medical School, the Wellcome Sanger Institute, the Max Delbruck Center for Molecular Medicine in Berlin and Imperial College, London. These teams and their collaborators analyzed about 500,000 cells from six different regions of the healthy adult human heart, using post-mortem organs from 14 donors. They examined RNA and protein expression and mapped the distribution of different types of cells in each region of the heart. In addition, they made comparisons of male and female hearts, and identified cells expressing genes known to be associated with different types of heart disease.
One of the take-home messages from this study is that there is a lot of cellular complexity in the heart – with 11 major cell types (examples include atrial and ventricular cardiomyocytes, fibroblasts and smooth muscle cells), as well as multiple subpopulations within each of those types. Also notable is the different distribution of cells between the atria (which are at the top of the heart and receive the blood) and ventricles (which are on the bottom of the heart and pump blood out): on average, close to half of the cells in the ventricles are cardiomyocytes, whereas only a third of the cells in the atria are cardiomyocytes. Finally, there is a significantly higher percentage of cardiomyocytes in the ventricles of women (56%) than in the ventricles of men (47%). The authors speculate that this latter difference might explain the higher volume of blood pumped per beat in women and lower rates of cardiovascular disease.
The authors gave a few examples of how their data can be used for a better understanding of heart disease. For example, they identified a specific subpopulation of cardiomyocytes that expresses genes associated with atrial fibrillation, suggesting that the defect may be associated with those cells. Similarly, they found that a specific neuronal cell type expresses genes that are associated with a particular ventricular dysfunction associated with heart failure. In addition, the authors identified which cells in the heart express the highest levels of the SARS-CoV-2 receptor, ACE2, including pericytes, fibroblasts and cardiomyocytes.
Now that these data are accessible for exploration at www.heartcellatlas.org, I have no doubt that many scientific explorers will begin to navigate to a more complete understanding of both the healthy and diseased heart, and ultimately to new treatments for heart disease.