University of Dundee

Greg Findlay group identifies key regulator of stem cell identity with implications for cardiac patients

17 Aug 2016

Scientists from the University of Dundee have discovered a key regulator of embryonic stem cell identity, research that could one day lead to new treatments for heart attack patients and those with congenital heart conditions.

Embryonic stem cells have the potential to provide tissue replacement therapies for a number of debilitating diseases due to their capacity to differentiate into any cell type in the adult body, a property known as pluripotency.

Globally, there is an extensive research focus into identifying new signalling pathways which control embryonic stem cell pluripotency and differentiation. To tackle this problem, a Dundee team led by Dr Greg Findlay worked with colleagues at Harvard Medical School.

They discovered that an enzyme called ERK5 promotes the transition of so-called naïve embryonic stem cells into the primed state, where they acquire the ability to differentiate. Through a combination of chemical engineering and genome editing strategies they confirmed that the ERK5 signalling pathway maintains cells in a state of naïve pluripotency. They were then able to show that ERK5 specifically regulates differentiation of embryonic stem cells to cardiac muscle cells, or cardiomyocytes.

The research is published in the latest edition of the Cell Reports journal.

Dr Findlay, of the University’s MRC-Protein Phosphorylation and Ubiquitylation Unit (MRC-PPU), said, “Our findings have significant implications for tissue regeneration. Most excitingly, we show that ERK5 inhibitors may instruct embryonic stem cells to form cardiac cells, which can be exploited to help repair damaged tissue following a heart attack.

“This enzyme acts like a switch. When ERK5 is switched on, it helps maintain embryonic stem cells, but when it is switched off these cells form heart tissue. Understanding the pathways that tell cells to turn into a particular type of tissue is a major challenge if we are to make the most of embryonic stem cells’ potential so this is very promising in terms of one day having new ways of treating heart patients.”

Dr Findlay’s lab are now looking to investigate the mechanisms by which ERK5 controls pluripotency and cardiac differentiation. They hope to significantly scale-up the research to the point where it can be shown to have potential benefits in clinical settings.

Professor Dario Alessi, Director of the MRC-PPU, said, “This very important paper provides significant new insights into the role that the ERK5 signalling pathway plays in biology. The ERK5 pathway has been a bit of a mystery and this study, defines a clear-cut role for ERK5 in controlling differentiation of stem cells.

“It has ramifications for how differentiated stem cell-derived lineages such as cardiomyocytes might be better produced in the future. I am also excited about how this opens up the potential to better understand the molecular mechanism by which ERK5 controls these pathways in future research.”