β-catenin-mediated human embryonic stem cell self-renewal and differentiation
Human embryonic stem cells (hESCs) can be maintained in culture indefinitely while retaining the capacity to generate any cell type of the body, therefore offering a potentially renewable source of cells for cell replacement therapy applications . hESCs also represent a platform for addressing some fundamental questions in basic biology, such as how stem cells retain the ability to produce more of themselves and how they give rise to more specialized cells. If the full potential of hESCs in both research and clinical application is to be realized, a greater understanding of the regulation of their fate is critical. Recently, we developed a new culture medium that allows us to efficiently propagate hESCs without loss of their potential to produce specialized cells. The key components in this culture medium are two small molecules that can modulate the function of β-catenin, a protein important for many cell functions. The main goal of this project is to understand how modulation of β-catenin’s function can control the fate of hESCs. Our study will be important not only for optimizing culture conditions for efficient and unlimited expansion of hESCs but also for manipulating and controlling the generation of specific cell lineages for use in regenerative medicine. Given that β-catenin is also a key player in the pathogenesis of diverse human cancers, our research is likely to identify novel β-catenin targets that could provide leads for anticancer drug development.
Currently, there is no cure or effective treatment for Parkinson’s disease, spinal cord injury, diabetes, cancers, and other pathological conditions. Many patients in California suffering from these afflictions could benefit from therapies using cells derived from human embryonic stem cells, which can give rise to any type of endogenous cell in the body. To realize clinical application of human embryonic stem cells or their derivatives, we must learn how to control the expansion of human embryonic stem cells, and more importantly, how to control the differentiation of human embryonic stem cells into specific cell types. Currently, human embryonic stem cells are routinely propagated on feeder cell layers, in medium containing serum or serum replacements whose components are incompletely defined. Consequently, the mechanism underlying human embryonic stem cell propagation and differentiation is still poorly understood. We recently developed new conditions that allow us to efficiently control the expansion and differentiation of human embryonic stem cells. In this study, we will further investigate how human embryonic stem cell fate is controlled under these conditions. Our study will be important not only for optimizing culture conditions for efficient and unlimited expansion of human embryonic stem cells but also for manipulating and controlling the generation of specific cell lineages for use in regenerative medicine.