Heart muscle cells (green) at the border of a wound in a zebrafish heart. Image credit: Fabian Kruse (CC BY 4.0)
Heart attacks are a common cause of death in the Western world. During a heart attack, oxygen levels in the affected part of the heart decrease, which causes heart muscle cells to die. In humans the dead cells are replaced by a permanent scar that stabilizes the injury but does not completely heal it. As a result, individuals have a lower quality of life after a heart attack and are more likely to die from a subsequent attack.
Unlike humans, zebrafish are able to regenerate their hearts after injury: heart muscle cells close to a wound divide to produce new cells that slowly replace the scar tissue and restore normal function to the area. It remains unclear, however, what stimulates the heart muscle cells of zebrafish to start dividing. To address this question, Honkoop, de Bakker et al. used a technique called single-cell sequencing to study heart muscle cells in wounded zebrafish hearts.
The experiments identified a group of heart muscle cells close to the site of the wound that multiplied to repair the damage. This group of cells had altered their metabolism compared to other heart muscle cells so that they relied on a pathway called glycolysis to produce the energy and building blocks they needed to proliferate. Blocking glycolysis impaired the ability of the heart muscle cells to divide, indicating that this switch is necessary for the heart to regenerate. Further experiments showed that a signaling cascade, which includes the molecules Nrg1 and ErbB2, induces heart muscle cells in both zebrafish and mouse hearts to switch to glycolysis and undergo division.
These findings indicate that activating glycolysis in heart muscle cells may help to stimulate the heart to regenerate after a heart attack or other injury. The next step following on from this work is to develop methods to activate glycolysis and promote cell division in injured hearts.
