The source of new cardiomyocytes during development and after injury has been revealed by University of California Los Angeles researchers who used fluorescent colored proteins to trace how cardiomyocytes are produced in mouse embryos. The findings could eventually lead to methods for regenerating heart tissue in human adults they report in a Nature Communications paper published yesterday.
"Our ultimate goal is to be able to regenerate cardiomyocytes after an injury like a heart attack," said Dr. Reza Ardehali, an associate professor of medicine in UCLA's division of cardiology. "But we're first trying to learn from the embryonic heart."
While it has been known that cardiomyocytes are formed during embryonic development, scientists have been unsure until now whether new cardiomyoctyes are only created when existing cardiomyocytes divide, or whether cardiac progenitor cells create new cardiomyocytes.
Ardehali and his colleagues, including Ngoc Nguyen, a UCLA graduate student and the study's co-first author, used four different fluorescent-colored proteins to determine the origin of cardiomyocytes. When the cells divide, the resulting "daughter" cells maintain the same color as the parent cell.
"The system lets us see, over time, which cell populations give rise to new cells," Nguyen said. "Compared to previous labeling methods that use only one or two different colors, this method allows us distinguish the role of different cells much more clearly."
The team labeled different types of starting cells—including cardiomyocytes and cardiac progenitor cells—in mouse embryos by engineering the cells to contain genes for the fluorescent proteins. They turned the fluorescent labels on at different times during embryonic development and then watched how the colors spread through the developing heart as the embryos grew.
The scientists found that during early in utero development, most new cardiomyocytes come from cardiac progenitor cells rather than from existing cardiomyocytes. As a mouse fetus develops, however, the cardiac progenitor cells lose their ability, over the course of a few days or a week, to generate new cardiomyocytes.
"Previously, researchers hypothesized that you have these progenitor cells until a set point in development, and then they turn into mature cardiomyocytes," Ardehali said. "We've shown that this process does not occur abruptly, but it is rather a gradual transition."
Image: UCLA researchers led by Dr. Reza Ardehali used four different fluorescent-colored proteins to determine the origin of cardiomyocytes in mice. Image courtesy of UCLA Broad Stem Cell Research Center/Nature Communications.