Chemical and Functional Genomic Approaches toward Understanding hESCs
Embryonic stem (ES) cells not only hold considerable promise for the treatment of a number of devastating diseases, they also provide an ideal tractable culture system of studying early embryonic development of all cell types. Harnessing these potentials of ES cells will require an improved ability to manipulate their self-renewal and differentiation, and a better understanding of the signaling pathways that control their fate.
Among many technical challenges to overcome, a robust self-renewal and clonal expansion condition for hESCs would be highly desirable, which would facilitate practical applications of hESCs toward therapies (e.g. large scale manufacture of desired cell types); provide a reliable platform for hESC engineering (e.g. genetic manipulation to create reporter or disease-specific model cell lines); and promote faster advance in basic understanding of hESC/developmental biology. Because the hESC field is still at its infancy, unbiased and functional discovery approach would be highly suited, e.g. providing tools and laying ground for scientific investigations. This proposal will integrate technology-driven approaches (for discovery of small molecules and genes that regulate hESC self-renewal and differentiation processes) and hypotheses that are derived from these discoveries for a better understanding and controlling of hESCs. Collectively, these proposed studies will provide new chemical tools, functional genomic technologies and substantial knowledge for better understanding and controlling hESC self-renewal and differentiation, and may ultimately allow development of therapeutics employing hESCs for treating diseases.
The proposed studies will provide new chemical tools, functional genomic technologies and substantial knowledge for better understanding and controlling hESC self-renewal and differentiation (e.g. development of robust self-renewal and clonal expansion conditions for hESCs) , and may ultimately allow development of therapeutics employing hESCs for treating diseases.