U of T researchers recently identified a new protein responsible for regulating development in mouse embryonic stem cells.
In an article published in Cell Stem Cell, PhD candidate Emily Walker found that the polycomb-like 2 (PCL2) protein modulates embryonic stem cell fate. This is the first time that the PCL2 protein has been studied in mammalian cells. In the absence of PCL2, embryonic stem cells undergo continual self-renewal and lose their ability to differentiate. Embryonic stem cell differentiation is essential to produce the many cell types that form our organs and tissues.
To understand the importance of PCL2 in stem cell development, Professor William L. Stanford, Canada Research Chair in stem cell bioengineering and functional genomics, along with his group identified the genes responsible for regulating PCL2 production, in particular, a gene target called Tbx3, which has been implicated in embryonic stem cell self-renewal.
In PCL2-deficient cells, self-renewal is impaired and looks very similar to cancer cell growth. Cancer cells not only divide continuously, but they also lose the ability to differentiate into appropriate cells and instead develop into a tumour.
Stanford’s group will consider the role of PCL2 in cancer cells, determining whether they express less PCL2 than normal cells and eventually search for drug treatments that rebalance PCL2 levels.
Another interesting application relates to induced pluripotent stem (iPS) cells, which are generated by taking a cell (such as a skin cell) and reactivating genes that are critical for embryonic stem cells. “Embryonic stem cells and iPS cells are unique and powerful because they have the potential to become any cell type in the adult body. This property allows for many applications in regenerative medicine as you could potentially use those cells to rebuild or augment any type of tissue,” explains Walker.
Researchers have succeeded in making iPS cells, but methods to improve efficiency are still being studied. Since removing PCL2 protein prevents embryonic stem cells from differentiating, researchers are now interested in the effect of PCL2 removal on a differentiated cell.
The advancement of stem cell research offers a myriad of medical uses, and people are already banking in on the potential opportunities. At birth, a baby’s umbilical cord is full of cord blood and is a rich source of stem cells. Organizations like the Cord Blood Bank of Canada offer parents the opportunity to preserve stem cells in the umbilical cord blood for potential use in the child’s future.
In addition, the Ontario Human iPS Cell Facility, co-directed by Stanford, focuses on creating iPS cells from patients with a variety of genetic diseases. These cells can then be used as a tool to study these diseases in the lab.
The identification of PCL2 as an important regulator of embryonic stem cells opens up a new chapter for scientific study. To better understand and characterize the nature of stem cells, more studies on PCL2, its effects on cancer cells and iPS cells need to be conducted.
