Some species, such as salamanders and zebrafish, are capable of reactivating programs of embryonic development following injury in order to regrow limbs and even major portions of vital internal organs. Since mammals share the same ability to conduct embryonic development, it is hoped that all of the necessary biochemical machinery to also conduct complete regeneration of organs still exists in adult mammals, merely suppressed in some way. Researchers investigate the exceptional regeneration of species like zebrafish in search of controlling mechanisms that might be manipulated to turn on the same exceptional regeneration in humans and other mammals. It remains to be seen as to how long this will take, and whether the options will be as straightforward as hoped for.
Humans can't regenerate heart muscle damaged by disease, but scientists have long known that some animals, such as zebrafish, can. The heart is made up of many kinds of cells that comprise muscle, nerve, and blood vessel tissue. A portion of these heart cells - in zebrafish, around 12 to 15% - originate from a specific population of stem cells called neural crest cells. Humans have analogous neural crest cells that give rise to varied cell types in almost every organ of the body, ranging from the facial skeleton to the nervous system. For some reason, zebrafish and a few other animals retain the ability as adults to rebuild tissues derived from the neural crest - the jaw, skull and heart, for example - while humans have lost that ability. These animals are not merely repairing damaged tissue, however. In the heart, cells around an injury revert to an undifferentiated state and then go through development again to make new heart muscle, or cardiomyocytes.
In the newly reported research, the scientists used single-cell genomics to profile all the genes expressed by developing neural crest cells in zebrafish that will differentiate into heart muscle cells. They then pieced together the genes expressed after they snipped away about 20% of the fish's heart ventricle. This procedure seemed not to affect the fish, and after about 30 days their hearts were whole again. By knocking out specific genes with CRISPR, they identified a handful of genes that were essential to reactivation after injury, all of which are utilized during embryonic development to build the heart. One in particular, called egr1, seems to activate the circuit first and perhaps triggers the others, suggesting a potential role in regeneration. The researchers also identified the enhancers that turn on these genes. Enhancers are promising targets for CRISPR-based therapies, since they can be manipulated to dial up or down the expression of the gene.
Link: https://news.berkeley.edu/2025/07/09/repairing-the-heart-if-zebrafish-can-do-it-why-not-humans/
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