Australasian Science: Australia's authority on science since 1938

Growing a Human Heart, One Embryonic Cell at a Time

Australian researchers have witnessed how human stem cells can be turned into heart cells after measuring changes in gene activity through the stages of heart development.

Unlike many tissues such as skin and bone, the heart does not have the capacity for self-repair after damage. This is one reason why heart disease is the leading cause of death worldwide.

To explore human heart development, the researchers chose to mimic how a heart develops in the embryo. “If we can get to grips with the complex choreography of how the heart builds itself in the first place, we’re well placed to find new approaches to helping it rebuild after damage,” said Dr Nathan Palpant of The University of Queensland Institute for Molecular Bioscience, who co-led the research published in Cell Stem Cell (https://goo.gl/Hj8zjB).

The team started with skin-derived human pluripotent stem cells that are capable of giving rise to any cell type in the body, and directed them to develop into heart cells. RNA sequencing catalogued exactly how individual stem cells transformed into mature heart cells. For each of 40,000 individual heart cells, the researchers measured the activity of about 17,000 genes.

“Each cell goes through its own series of complex, nuanced changes,” said research co-leader A/Prof Joseph Powell of the Garvan-Weizmann Centre for Cellular Genomics. “They are all different, and changes in one cell affect the activity of other cells. By tracking those changes across the different stages of development, we can learn a huge amount about how different subtypes of heart cells are controlled, and how they work together to build the heart.”

The team found that the HOPX gene is essential for controlling how the heart grows bigger – a process known as hypertrophy. HOPX functions like a toggle switch that controls a critical decision point in heart development: the change from heart cells that are immature (and still dividing) to heart cells that no longer divide but are bigger and more mature. This finding will help researchers learn more about the processes that underlie congenital heart disease, and may provide a new strategy for controlling heart regeneration.

The HOPX findings also shed light on the conditions required to encourage stem cells to develop into mature heart cells. This will support researchers to grow mature heart cells accurately and reliably in the lab.

“We are now building on the knowledge gained from this work to investigate at what stages during heart development, and in what cell subtypes, the genetic risks of cardiovascular disease become most dangerous,’’ Powell said.