Combinatorial roles of transcription factors, signaling, and miRNAs in naive pluripotency
Embryonic stem cells can be expanded indefinitely in a culture dish and have the potential to make any cell type in the adult body. These properties make them a remarkable tool to study and even potentially treat human disease. However, most of what we know about embryonic stem cells is based on the mouse model. Human embryonic stems are inferior to their mouse counterparts in a number of ways including more complex culture conditions, increased genetic instability, diminished manipulability, and likely diminished developmental potential. Much work has suggested that the differences between human and mouse embryonic stem cells is their developmental maturity. Therefore, there is a push to find ways to induce these cells to a less mature state, more similar to that of mouse. This application presents preliminary data showing novel means to do exactly that. Here we propose to characterize the resulting cells and find additional means that could synergize to further induce a stable immature embryonic stem cell fate. Such cells will be tested for all the desired properties one normally finds in the equivalent cells in mouse. Successful completion of these aims would have a dramatic impact on the stem cell field as it would provide more robust means for laboratories and companies around the world to grow and differentiate human embryonic stem cells into genetically sound adult cell types for the study and treatment of a wide range of human diseases.
The proposed research aims to improve the utility of human embryonic stem cells through a deeper understanding of the mechanisms that control their growth and their potential to make all adult tissue types. Successful completion of the research would lead to more robust methods of expanding, manipulating, and differentiating the cells. Such advances are critical to extending the promise of embryonic stem cells in both the study and treatment of disease. Therefore, it will benefit the State of California by making human embryonic stem cells more experimentally accessible to both academics and industrialists. The knowledge learned is expected to provide insights useful to the development of new technologies by California laboratories and companies. Such technologies would have major implications for the development of new commercial endeavors and for the improvement of human health, both major goals of the California Institute of Regenerative Medicine.