Kursad Turksen, PhD
kturksen@ohri.ca
The Development and Maturation of Skin Cells
"What are you going to be when you grow up?" This question is frequently put to children, but it has a biological parallel. Just like people, body cells grow up to do many different jobs, and the mystery of how an undifferentiated cell becomes a specialized muscle, blood, skin, bone, or nerve cell has intrigued scientists for decades. While the ways in which specialized cells differ from each other may be clear, what induces each cell down its particular pathway of development is still largely unknown. Dr. Kursad Turksen is studying this question in skin cells and hair follicles, in order to determine the steps by which an undifferentiated cell becomes a fully mature skin cell.
Dr. Turksen's starting point is to identify what he calls the "commitment genes" along the pathway. These genes direct undifferentiated and progenitor cells to start the process of becoming one specific organ or another, much as a guidance counselor might say "be an engineer," or "be a teacher." Each step taken leads to the branching out of more choices. For example, stem cells or early progenitors of skin cells have begun to commit themselves. There are very few of them, but they have a high proliferative capacity. They have selected the pathways and are already epidermal cells, but they must still go farther along the skin pathway, and are not yet mature skin cells. The closer the cells get to maturity, the more restricted they become, with a limited proliferative capacity. From the point at the end stages of skin cell maturation, where they have become committed skin cells, the stages of differentiation are reasonably well known.
Through a technique called "gene trapping," Dr. Turksen is currently working to identify the genes that direct undifferentiated cells or early progenitor cells to become mature skin cells. Dr. Turksen likens this project to a fishing expedition. He is certain the genes are there, and will be easy to recognise when he identifies them, but beyond that he knows nothing about them, even whether only one or 5,000 different genes are involved. However, the overall pathway the genes direct these cells down is something that he has researched over the past few years, and now understands rather well. The identity of the genes themselves represents something of a missing link.
To find them, Dr. Turksen is using a type of cell that has become popular in the last few years called totipotent stem cells. As long as they are kept in culture under proper conditions, totipotent cells don't differentiate. In recent years, different researchers have induced these cells into specific pathways to become neurons, blood cells, cardiac muscle cells, or fat cells. Once Dr. Turksen isolates the genes involved, he should be able to direct totipotent cells to become skin cells.
This research has some important implications. The ability to grow skin will help in the treatment both of severe burns and skin cancer, saving many patients currently beyond our ability to help. Furthermore, the malfunctions that lead to squamous or basal cell carcinoma will be better understood, perhaps making it possible to prevent them, if we understand the regulators of cell growth.
Another area that will benefit is the treatment of psoriasis. Although this disease strikes only about 1% of the world's population, it can be so severe in some cases that its victims become psychologically and socially isolated. It seems that in psoriasis the cells don't recognise the signals to differentiate, but instead keep proliferating and pile up, creating thick, flaky, itchy, red areas of skin. If these areas cover a large portion of the body, the disease is debilitating. Currently, there is no cure, although psoriasis can be controlled for a short time.
Knowledge of how skin cells mature will also illuminate the process of wound healing, which is now understood only in a general sense. An interesting property of skin is that it loses its ability to heal without scars as soon as a person is born. If a way could be found to resurrect the scarless repair mechanism that unborn babies possess, it would be of obvious interest to those facing major surgery.
While most people's health worries tend to focus on heart attacks or cancer, Dr. Turksen points out that they spend more money on maintaining and improving their skin and hair than on anything else. That makes it all the more ironic that we tend to take for granted the health of something that's often referred to as the body's largest organ. As Dr. Turksen reveals the complexities of skin development, we can look forward to new hope for those who suffer from skin diseases.
