A master cell in human heart development
Dr. Kenneth Chien, North American coordinator of the Heart Progenitors in Cardiovascular Disease and Development network, and colleagues have identified a master cell in the developing human heart. The investigators had previously found, in mice, that cells expressing a protein called Isl1 could give rise to different types of heart tissue, but the relevance of this finding to the more complex development of the human heart was unclear. The protein Isl1 is a transcription factor, acting in the cell nucleus to turn genes on or off.
In the July 2, 2009 issue of Nature, Dr. Chien and his team report that human fetal hearts also contain cells expressing the Isl1 protein. These cells have to ability to self-renew and expand in number, characteristics of master progenitor cells. Using genetic techniques, the investigators tracked human Isl-expressing cells over time and found that, like their counterparts in the mouse, they give rise to three tissue types: the muscle responsible for the pumping action of the heart, the smooth muscle surrounding blood vessels, and the endothelium that lines the inside of blood vessels.
The identification of this important master cell has numerous implications for the understanding of heart development and disease, as well as for future treatments. While it is unlikely that a complete heart could be regenerated from Isl1-expressing cells, this discovery may lead to the generation of specific tissues, such as heart muscle, which can be used as “patches” to repair areas of damage. Moreover, such human tissues could serve in the screening of new drugs for positive and negative effects. Their use would serve as an important complement to animal studies in providing important information about a drug’s effects before testing it in patients.
Because the cells expressing Isl are located in regions of the heart where congenital defects are commonly found, this finding also may lead to better understanding of the causes of congenital heart disease.
This research was also supported by the Harvard Stem Cell Institute.
Click on the title to access the article in Nature: Human ISL1 progenitors generate diverse multipotent cardiovascular cell lineages.