Researchers have discovered a gene in zebrafish so powerful it can be used to redirect the fate of cells in the developing embryo to become beating heart cells, suggesting that a similar gene in humans could be used to generate heart cells in culture for transplant in ailing people.
The finding, the first discovery of a so-called "master" gene for myocardial, or heart muscle, cells in an animal model, puts researchers on track for exploring the capability of homologous genes in mice and humans.
The gene, known as gata5, acts in embryonic cells, which are primordial, unspecialized cells that form in the earliest stage of embryonic development and are genetically programmed to evolve into one of many specialized cell types, such as skeletal muscle cells, nerve cells, blood cells, skin cells, and liver cells.
Normally, the gene acts only in those embryonic cells destined to become myocardial cells. The research shows, however, that gata5 can reprogram otherwise predestined embryonic cell types to become beating heart cells.
If zebrafish gata5, or its human equivalent, could prompt a particular type of embryonic cell, known as a human embryonic stem cell, to become a beating heart cell, researchers could theoretically use this technique to cultivate and harvest such genetically modified cells in the petri dish and then transplant them into people with failing hearts.
"Discovery of a gene that could convert human embryonic stem cells into myocardial cells would be golden," said Didier Stainier, PhD, UCSF assistant professor of biochemistry and biophysics, the senior author of the UCSF study and a pioneer in the study of heart development in the transparent zebrafish embryo. "Gata5 is potentially such a gene. It appears to be sufficient to drive the entire myocardial program in certain cells not normally fated to contribute to the heart."
Gata5's capability produces dramatic images