Mechanisms of NANOG Function in hESC
Human embryonic stem cells (hESC) have been proposed as a renewable source of tissue for regenerative medicine applications. One obstacle to the development of hESC based therapies is that hESC spontaneously and randomly differentiate (or change) into non-specific cell types in the laboratory. The main reason for this random differentiation is that we don’t completely understand the basic biology of these cells and mechanisms that keep the stem cells renewing themselves in the lab (called self-renewal). In fact the most reliable method to keep human embryonic stem cells alive in the laboratory is to culture them on cells taken from mouse embryos. This techniques requires a significant amount of time to make these mouse cells and test them, as well as leading to significant batch-to-batch variety in quality, as well as the possibility of introducing animal viruses or other pathogens.
In the proposed studies, we will investigate one gene that we know is very important for stem cells to make more stem cells (self-renew)- called NANOG. Despite the importance of NANOG to stem cells, there is relatively little know about the physical structure of this gene or protein, or how it works, and what other genes and proteins it interacts with to keep stem cells renewing. We will then use the data generated in our studies to generate specific growth or ‘self-renewal’ factors that can be added to the embryonic stem cells and reliably keep them undifferentiated. If successful, the development of such growth factors will make all aspects of human embryonic stem cell research more reliable and efficient. This in turn will increase the time that researchers have to developing therapeutic protocols, rather than spending a large amount of their time and energy to keep their cells alive and renewing. Furthermore, it will facilitate the scale-up of stem cell applications from small scale laboratory studies. Thus, our studies have the potential to impact on all human embryonic stem cell research, and increase the rate of development of all stem cell based therapies. The development of a growth factor(s) that can replace mouse cells, and reliably keep the stem cells alive would prove very useful to stem cell researchers, as well as increase the safety of the cultures for therapeutic purposes.
One of the biggest hurdles in human embryonic stem cell research is that the cells spontaneously and randomly differentiate into a variety of non-specific cell types in culture. These non-specific cell types have little, if any, therapeutic potential. It requires a high degree of technical training to minimize this random differentiation, and even then is not preventable with currently available growth factors and techniques. Our project will study the biological processes that keep stem cells renewing. We will then use this information to evaluate new growth factors that will keep human embryonic stem cells in an undifferentiated state. If successful, these growth factors will increase the efficiency of all human embryonic stem cell research, by dramatically decreasing the amount of time spent keeping human embryonic stem cells alive and undifferentiated. In turn, this will allow researchers to spend more time and effort developing stem cell therapies for human disease, and increase the rate of development of stem cell therapies .