Scientists at Sanford-Burnham have uncovered the critical switch that directs stem cells to become heart-muscle cells. Until now, the central mechanism that instructs cells to become heart muscle has remained obscure. The study, published in Genes & Development, shows how a particular signal from outside the cell activates genes that make stem cells become cardiomyocytes.
“Today, we can’t create new muscle for individuals with damaged hearts. The only way to replace damaged muscle is a heart transplant,” said Mark Mercola Ph.D., professor in the Sanford Children’s Health Research Center and director of the Muscle Development and Regeneration Program at Sanford-Burnham. “Our goal is to understand the process that helps heart cells repair themselves and to develop drugs that encourage the process—potentially bypassing the need for heart transplants.”
In a collaborative effort with the lab of Pier Lorenzo Puri, M.D., Ph.D., the researchers found that blocking transforming growth factor beta (TGF-beta)—a protein that controls cell proliferation and differentiation—instructs stem cells to turn on muscle-specific genes, thereby directing them to become heart muscle rather than other cell types.
Blocking TGF-beta has a very specific effect on the stem cell’s DNA, altering the three-dimensional structure of the chromosomes to “open up” at the positions of muscle genes so that they become available to the machinery that reads the genetic code and produces muscle-specific proteins.
Puri’s lab had been working on the nuclear machinery that remodels chromosomes structures, while Mercola’s lab was working on the molecular signals that direct heart-muscle development. By combining efforts, the scientists linked the key extrinsic factors that direct stem cells to chromosomal remodeling, and thus defined the “switch” that turns stem cells into muscle cells.
The implication for heart disease is that it might be possible to activate the same process using drugs that block TGF-beta and boost a heart’s capacity to heal itself. Indeed, Mercola’s group has developed such a potential drug, published last year in Cell Stem Cell and now in trials in animal models of myocardial infarction.
Puri is an associate professor in the Sanford Children’s Health Research Center and the Muscle Development and Regeneration Program at Sanford-Burnham.
About Heart Disease
According to the Centers for Disease Control and Prevention, heart disease is the number one cause of death for men and women in the United States, claiming over 600,000 lives each year. The total cost of heart disease is estimated at over $100 billion annually, including doctors, hospital services, medications, and lost productivity.