Fabian Kruse from the Bakkers group will defend his thesis “Mending broken hearts – Cardiac regeneration in zebrafish” on August 31. In his thesis he studies heart regeneration in the zebrafish.

Cardiovascular disease
Cardiovascular disease is the leading cause of death in the world, causing more than 30% of all deaths. In case of a heart infarction, part of the heart dies, because no longer receives enough blood, and therefore oxygen. In humans, a scar is formed in this area, but the heart tissue does not grow back. This scar makes sure that the heart stays intact, but scar tissue is rigid tissue that cannot pump with the rest of the heart. Therefore, the heart is less able to pump blood through the body.

Zebrafish can regenerate their heart
In his thesis, Kruse describes the results of 5 years of research into heart regeneration in the zebrafish, after an injury that is similar to a heart infarction in humans. The zebrafish is used as a model for this, since zebrafish are able to regenerate their heart completely after part of the heart dies. The scar, that is also formed in the zebrafish, is slowly replaced by functional heart tissue. To study the regeneration process, Kruse applied two techniques: tomo-seq and single-cell sequencing.

Tomo-seq
Tomo-seq is a method that was developed by the Van Oudenaarden group at the Hubrecht Institute. Using this method, Kruse sliced the wounded zebrafish hearts in very thin slices and investigated the gene expression in each of these slices. This enabled him to get more insight into which processes and signalling pathways are active in the various areas of the regenerating heart: the injury area, the border zone and the remote healthy myocardium. Kruse found that a certain signalling pathway, the BMP-pathway, is more active in the border region and that this pathway is important for the regeneration of the heart, because it enhances the proliferation of heart muscle cells.

Single-cell sequencing
Even though the heart slices studied with tomo-seq are very thin, they still contain multiple cell types, which makes it impossible to determine which cells contribute to which processes. To study this, Kruse used single-cell sequencing, in which gene expression is studied in single cells. Kruse discovered that those heart muscle cells that contribute to the regeneration of the heart change back to a more embryonic state. It is known that embryonic heart muscle cells are much more capable of proliferating than adult heart muscle cells. This explains why specifically these cells are able to contribute to heart regeneration.

Insights into heart regeneration
Kruse’s research generates more insight into the reasons that zebrafish can regenerate their heart while humans cannot. If we, in the far future, would be able to stimulate human heart muscle cells in such a way that they change back to a more embryonic state, these cells might be able to contribute to the healing of the heart after a heart infarction.