Role of Notch signaling in human embryonic stem cell differentiation to neuronal cell fates
Human embryonic stem cells (HESCs) are capable of giving rise to a variety of differentiated human cell types that in principle could be used therapeutically to treat tissue damage that arises in human disease. The promise of HESCs is still quite limited because of technical limitations in our ability to propagate these cells in culture, while retaining their potency to become many different types of cells, and to guide them to become the right type of cell needed for clinical use. The proposed work will develop the tools to address these issues, by focusing on the Notch signaling pathway. Studies of the Notch pathway in model organisms like mice has shown that it plays a pivotal role in regulating the development of embryonic cells, by activating critical target genes that maintain cells in a proliferative, undifferentiated state. The proposed experiments will examine the activity of the Notch pathway in HESCs, as they are experimentally induced to form the precursors to nerve cells. The long-term goal of this work is to develop the information and tools needed to manipulate HESCs in culture via the Notch pathway, allowing one to better control their proliferation and differentiation into defined cell types.
The goal of the proposed research is to develop tools that can be used to manipulate human embryonic stem cells, thus allowing them to be more effectively used as therapeutic agents. The process we are studying will help define optimal procedures to encourage human embryonic stem cells to produce homogeneous populations of specific neural cell types that are needed to replace damaged neural tissues for patients with Parkinson’s and other neural diseases.