Heart stem cells labelled red, green & white in a mouse embryo: Wellcome-MRC Cambridge Stem Cell Institute.
Taking heart: research shows how heart cells are born
26 Jan 2018
Scientists have pinpointed for the first time which specific cells in an early embryo will go on to become heart cells. The researchers hope that understanding how heart stem cells develop could help scientists to develop new therapies for infants born with hereditary heart conditions.
Teams at the Wellcome – MRC Cambridge Stem Cell Institute at the University of Cambridge and the Université Libre de Bruxelles used pioneering technology to measure the genetic activity of the earliest heart progenitor cells present in a mouse embryo. Their research, published in the journal Science, took advantage of a cell labelling strategy based on a gene called Mesp1, which is critical for directing stem cells to become cardiac cells in the developing heart. Using powerful computer analysis, the researchers could identify the distinct progenitor cell populations that would go on to develop into the specific cell types required for a fully functioning heart.
Stem cells in the developing embryo have the extraordinary ability to become any type of cell in the body, with the process of development following set pathways controlled by our genes. The heart is the first organ to develop in the embryo and strict genetic instructions control the production of the different cell types that allow the heart to function (such as cardiomyocytes that control the pumping of the heart and pacemaker cells that control the timing of the heartbeat). If this process is disrupted severe heart defects occur, including congenital heart disease which affects nine in every 1,000 infants born in the UK.
Professor Cédric Blanpain at the Université Libre de Bruxelles, one of the lead researchers involved in the study, explained: “This new analysis shows that cardiovascular stem cells in the embryo are already “primed” to give rise to all the different types of heart cells, such as cardiac muscle cells or pacemaker cells. Understanding the genetic features associated with early cardiovascular cell lineage commitment will be important in designing new strategies to manage and treat congenital heart disease”.
Professor Bertie Göttgens from the Wellcome – MRC Cambridge Stem Cell Institute added: “Our new discoveries critically depend on recent technological innovations that now allow us to determine the gene activity in individual single cells. Not only can we study tiny cell populations which wasn’t possible before, but we can also use the computer to separate the individual single cells into subgroups or cell types, based on their gene activity profiles. From these newly discovered gene profiles, we can discover new candidate genes that may be exploited for developing new therapies to repair the heart”.
Dr Nathan Richardson, MRC Head of Molecular and Cellular Medicine, said: “These new findings provide exciting insights into the complex development of the heart from progenitor cells. Crucially they also open the way for opportunities to develop new treatments for heart disease, and demonstrate the value of the MRC’s long-term commitment to stem cell research and discovery science.”
The researchers now plan to continue this cutting-edge research to discover the precise molecular defects that occur during the earliest stages of heart development in models of congenital heart disease. This they hope will pinpoint new targets for developing better therapies to repair and regenerate the heart.
The research was supported by Wellcome, MRC, Bloodwise, Cancer Research UK, National Institutes of Health*, FNRS, the ULB foundation, the foundation Bettencourt Schueller and the Leducq Fondation are gratefully acknowledged by the team.