Last week, scientists gave us exquisite images of three of our body’s most important organs, detailed like never before. From neighborhoods of intestinal cells to the architects of new life, we saw how cells are arranged and interact.
Now a group of scientists has produced what they claim is the most detailed cell catalog of the human heart, including the specialized tissue where the heartbeat originates.
A part of Atlas of Human Cells consortium, which aims to map every cell type in the human body, researchers from several UK and German institutes mapped eight regions of the human heart and profiled 75 different cell states that keep the heart moving and help defend it against infection.
The map is not something most of us can visually appreciate. It is more like a molecular catalog of cell types and their active genes, and it can help understand diseases such as those that affect heart rhythm.
As we can feel inside our beating chests, the heart is muscles in motion and electrical impulses in action. Heart contractions are the result of the collective movement of heart muscle cellstriggered by electrical impulses in so-called pacemaker cells.
These pacemaker cells are mostly found in the sinoatrial node of the heart, part of the cardiac conduction system that includes a few other interconnected nodes and bundles of cells that scientists don’t fully understand.
“The cardiac conduction system is essential for the regular and coordinated beating of our hearts,” explains James Cranley, a cardiologist specializing in heart rhythm disorders and joint lead author of the study. “Yet the cells that make it up are poorly understood.”
To resolve these cell types in more detail, Cranley and colleagues used single-cell transcriptomic methods, which decipher how the genetic instructions encoded in DNA are read in individual cells.
They applied these methods to tissue samples from 25 donor hearts that were not entirely suitable for organ transplantation, but invaluable for this study, which analyzed more than 700,000 individual cells and nuclei.
By mapping different clusters of heart cells in several donors who were otherwise healthy, the team discovered pacemaker cells in close association with glial cells.
Glia normally support neurons in the brain and the wider nervous system. However, in the sinoatrial and atrioventricular nodes and atrioventricular bundle of the heart, the researchers found glial cells that support signaling processes in pacemaker cells.
The pacemaker cells were ‘shrouded’ in the slender extensions of the glial cells, and their connections resembled how nerve cells come together at synapses.
The researchers also examined the outer layer of the donor hearts. There they found immune cells called plasma cells and confirmed that they produce antibodies to protect the heart from infections in the nearby lungs.
With the myocardium, the heart’s muscle tissue, Cranley and colleagues identified a population of cells that appear to be particularly sensitive to stress and inflammation.
The cells had lots of genes that code for receptors for inflammatory signaling molecules and expressed high levels of a peptide that has been associated with heart failure.
“By understanding these cells at an individual genetic level, we can potentially develop new ways to improve cardiac treatments,” say joint lead author Kazumasa Kanemaru, a cardiac genomics researcher at the Wellcome Sanger Institute in the UK.
In addition, the researchers categorized pacemaker cells based on the types of ion channels they express, hoping that their findings can further research into what happens when the heart’s conduction system false teethand why some cardiac therapies do not work as intended.
Ion channels are cellular gatekeepers that allow charged molecules to flow in and out of cells. This brief polarization triggers all important electrical signals in pacemaker cells that start the heart.
“Together, these data provide a very specific map of genes and cells in the (cardiac) conduction system,” the researchers conclude.
The study is published in Nature.