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.
The human cell atlas
Similarly, technological advances have enabled scientists to map human tissues and organs at a level of detail that was previously unimaginable.
Scientists can profile hundreds of thousands of single cells in parallel, examining RNA and protein expression. 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 provide a much better understanding of the biology and physiology of normal human tissues, offer new insights into the diseases that affect those tissues, and point the way to developing new therapies.
The human heart
One example of this new breed of cartography was published September 24 in the journal Nature in a paper simply titled “Cells of the Human Heart”.
Scientists from Harvard Medical School, the Wellcome Sanger Institute, the Max Delbrück Center for Molecular Medicine in Berlin, and Imperial College London led this tour-de-force effort. 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 cell types in each region of the heart. In addition, they compared male and female hearts and identified cells expressing genes known to be associated with different types of heart disease.
Complexity
One key takeaway is the heart’s remarkable cellular complexity, with 11 major cell types and multiple subpopulations. The atria and ventricles also differ: about half the ventricular cells are cardiomyocytes, while only a third of atrial cells are. Women have more ventricular cardiomyocytes (56%) than men (47%), which may explain their higher stroke volume and lower cardiovascular disease rates.
The authors showed how these data can clarify heart disease. They found a cardiomyocyte subpopulation expressing genes linked to atrial fibrillation, suggesting those cells drive the defect. They also identified a neuronal cell type expressing genes tied to a ventricular dysfunction associated with heart failure. In addition, they pinpointed which heart cells express the highest levels of the SARS‑CoV‑2 receptor ACE2, including pericytes, fibroblasts, and cardiomyocytes.
With these data now available at http://www.heartcellatlas.org, many researchers can explore the healthy and diseased heart in greater depth and move toward new treatments.