“Stem cells arise early in the gestation process, then start developing into approximately 250 different types of adult cells, including neurons, skin, stomach and heart cells,” said Lluis Morey, Ph.D., a member of the Cancer Epigenetics Program at Sylvester and research assistant professor in the Dr. John T. Macdonald Foundation Department of Human Genetics. “Our collaborative international research team looked at how Polycomb proteins dictate these decisions for cardiac and cartilage cells.”
Morey was lead author of “Polycomb Regulates Mesoderm Cell Fate-Specification in Embryonic Stem Cells through Activation and Repression Mechanisms,” an article published in the scientific journal Cell Stem Cell. The study was done in collaboration with Benoit G. Bruneau, Ph.D., professor of pediatrics at the University of California San Francisco School of Medicine, and a worldwide expert on cardiovascular research, along with co-authors from research institutes in Barcelona and San Francisco.
Morey’s study noted that the Polycomb group of complexes (PcG) is implicated in cancer, as well as the normal development of stem cells, and that different Polycomb genes might exert specific functions during development. For instance, the Bmi1 Polycomb promotes neural stem cell self-renewal, while the over-expression of other Polycomb proteins has been found in several types of cancer.
Morey added that until this study, little was known about the Polycomb mechanisms that determine the fate of embryonic stem cells, whose three layers — ectoderm, mesoderm and endoderm — give rise to differentiated adult cells. For example, the ectoderm layer affects the genetic expression of neurons and skin cells, while the endoderm layer impacts intestinal cells, and the mesoderm layer drives the creation of cardiac and cartilage cells.
“When the Polycomb genetic regulator Mel 18 was deleted in the laboratory, the mesoderm stem cells could no longer develop into cardiac cells,” Morey said. “Interestingly, cells from the ectoderm lineage, like neurons, remained unaffected. This study provides a new perspective on the activation of genes during the cardiac cell differentiation process. It also indicates that Mel 18 might also be specifically associated with heart disease, providing a direction for future studies.”
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