Getting straight to heart cells with stem cells

The development of embryonic stem cells into heart cells is a complex process involving the precisely scheduled activation of several molecular pathways and involves at least 200 genes in this process of conversion. Researchers have found a simpler way which involves inactivating a single gene.

The work offers scientists a streamlined method to arrive at functioning heart cells (cardiomyocytes) for both research and regenerative therapies.

This discovery is really impressive because it means we can potentially create a reliable protocol for taking normal cells and moving them very efficiently from stem cells to heart cells. Researchers and commercial companies want to easily generate cardiomyocytes to study their capacity for repair in heart attacks and disease , this innovation brings us one step closer to being able to do that.

In 2015, Researchers which studies proteins that manage cell growth and development, discovered that two different cellular processes cooperate to enable embryonic stem cells (ESCs) to develop into specific cell types like pancreas, liver and heart. The team found that the Wnt pathway loads up the cellular machinery to begin copying and activating genes, and then the Activin pathway ramps up that activity many fold. Together, the two pathways direct stem cells to an intermediate stage from which they further progress into cells of specific organs. By exposing the cells to a signaling molecule at two different timepoints, the team could trigger first Wnt, then Activin, and end up with specialized cells.

In the process of their experimentation, researchers discovered a third pathway governed by a protein called YAP, which seemed to put the brakes on the Activin pathway, thereby keeping stem cells from specializing.

Wanting to better understand this effect, in the current work researchers set out to manipulate the YAP gene in various ways to see what would happen. They began by using the molecular scissors known as CRISPR-Cas9 to cut the gene out of ESCs' DNA. So, they could no longer make the YAP protein. Then the duo exposed the cells to the signaling molecule to see what, if anything, happened.

To their great surprise, the cells went fromthe stem cell stage directly to beating heart cells.

Instead of requiring two steps to achieve specialization, removing YAP cut it to just one step. That would mean a huge savings for industry in terms of reagent materials and expense.

Intriguingly, further analysis revealed that the same genes were being turned on as would be activated via the normal Wnt-Activin stem-cell specialization process.

This revealed to us a hidden, specific cellular lineage directly to beating cardiomyocytes.  It's both fascinating and medically and commercially useful to find genes that are differently regulated still lead to the same result. Because removing a gene entirely can have unintended effects, the team next wants to test whether they can turn off the YAP gene using small commercially available inhibitor molecules, and still derive functioning cardiac cells from stem cells.

Meet Us at 28th International Conference on Cardiology and Healthcare in Abu Dhabi, UAE for more recent updates in cardiology research.

For details contact:
Aurora Lorenz
Program Manager-Cardiology Care 2018
Mail:cardiology@healthconference.org; 
healthcare@cardiologyconference.org
Website: https://healthcare.cardiologymeeting.com/