Stem cells have the potential to become any kind of cell. This flexibility is what makes them so intriguing to medical scientists who hope to harness this potential to generate new cell therapies. Over the past few decades, scientists have demonstrated that they can coax stem cells to become skin cells, muscle cells, and brain cells – to name just a few. In theory, we have good reasons to believe that stem cells have the capacity to replace any damaged cell in the body. In practice, however, there are two very difficult questions that continue to challenge scientists. First, how do you get stem cells to make the exact cell type that you need, such as a light-sensing photoreceptor? And second, how do you get these new replacement cells to function inside human bodies?
FFB-funded scientist, Dr. Michel Cayouette, is focused on the first question. For years, he has been trying to figure out how stem cells become photoreceptors, the eye’s light-sensing cells. The loss of photoreceptors leads to blindness in a variety of different eye diseases, including age-related macular degeneration and retinitis pigmentosa.
Dr. Cayouette’s recent discovery is garnering widespread attention because it was featured on the front cover of the prestigious scientific journal: Developmental Cell. The project was carried out in collaboration with the group of Dr. Stéphane Angers, Associate Professor at the University of Toronto. Together, they offered new key insights about how so many different kinds of neural cells, such as photoreceptors, are created during the development of the nervous system.
In order to multiply and generate new tissues, stem cells divide into two daughter cells, which are not necessarily identical: the daughter cells can differentiate to produce various cell types that are essential to proper tissue function. This is called cell diversification. However, the factors that drive daughter cells to be identical or different is poorly understood by scientists. To investigate this phenomenon, Dr. Cayouette’s team at IRCM tested if the orientation of stem cell division impacts cell diversification.
To illustrate why the direction of cell division matters, imagine a pizza that is half cheese and half pepperoni. Now imagine that you are going to cut this pizza in half. Depending on where you make the cut, you could end up with one half that is only cheese and one half that is only pepperoni – or, you could end up with two equal halves, which both have a mix of cheese and pepperoni.
The researchers demonstrated that a gene named SAPCD2 influences cell division orientation. Moreover, they confirmed that the orientation of division controls daughter cell fates in vivo. To do this, they studied mouse retinal stem cells that were genetically engineered to express or not the SAPCD2 gene. When the cells are expressing SAPCD2 they divide into two identical daughter cells (i.e., two equal halves of cheese and pepperoni), but when you take SAPCD2 away, it changes the direction that they are dividing and instead results in two different daughter cells (i.e., one half cheese only and one half pepperoni only). These results demonstrate that SAPCD2 controls stem cell division orientation, which in turn affects cell diversification.
This discovery will help researchers who are working to program stem cells into specific cell types of interest, such as photoreceptors, the light-sensing cells that degenerate in diseases causing blindness. For example, researchers are developing methods to generate large quantities of photoreceptors from stem cells to use in transplantation studies. Perhaps manipulating the SAPCD2 gene will help researchers’ efforts to generate pure populations of photoreceptors.