Collaborating researchers from around the world found four Id genes that have long been known for their activity in neurons and blood cells are also linked to heart development. These genes help tell undifferentiated stem cells to form heart tubes and then, eventually, muscle. The study was published in the journal Genes & Development earlier this month from researchers at the Sanford Burnham Prebys Medical Discovery Institute (SBP), the Cardiovascular Institute at Stanford University, the International Centre for Genetic Engineering and Biotechnology, the University Pierre and Marie Curie, and the University of Coimbra in Portugal.
In these studies, the scientists used CRISPR to knock out all four Id genes in mice and found that the mouse embryos developed with no hearts at all. Further study showed Id genes enable heart formation by turning down the Tcf3 and Foxa2 proteins, which inhibit the process and turning up Evx1, Grrp1 and Mesp1, which support the process.
"It has always been unclear what intra-cellular mechanism initiates cardiac cell fate from undifferentiated cells," says Alexandre Colas, Ph.D., assistant professor in the Development, Aging and Regeneration Program at SBP and corresponding author on the paper. "These genes are the earliest determinants of cardiac cell fate. This enables us to generate unlimited amounts of bona fide cardiac progenitors for regenerative purposes, disease modeling and drug discovery."