Human oocyte development for genetic, pharmacological and reprogramming applications
There is much excitement over the possibility of new and fundamentally-different therapeutic applications for human embryonic stem cells and the cells to which they differentiate. In addition, there is equally great excitement in the scientific community regarding the potential of human embryonic stem cells for biological studies of how different human cell types differentiate into normal and diseased tissues. To date, there are more than 400 human embryonic stem cell lines that have been reported to have been derived from human embryos that are donated for research due to lack of suitability for transfer for reproduction or being in excess of the needs for reproductive purposes. The methodology to derive new human embryonic stem cell lines was largely derived from years of work in the clinic that resulted in optimal conditions to grow human embryos and from years of work in animal species, mostly the mouse. In spite of this great progress, we have not, however, yet derived chromosomally-normal (genetically-normal) human embryonic stem cell lines via reprogramming techniques such as somatic cell nuclear transfer. In part this is due to the inaccessibility of human oocytes or eggs for potential therapeutic and basic science applications. In this proposal, we seek to differentiate human oocytes/eggs from multiple hESC lines and use them to reprogram somatic cell DNA. Specifically, we will: 1) Assess and compare the ability of multiple nonfederal hESC lines to contribute to the germ cell lineage (form immature oocytes). 2) Differentiate hESCs to mature oocytes/eggs. 3) Assay the ability of oocytes derived in vitro, relative to immature oocytes donated for research, to reprogram a somatic nucleus. We expect to successfully complete this research with the end results contributing to the improvement of current assisted reproductive practices such as IVF, and improved ability to detect errors in oocytes that lead to birth defects. In addition, since oocytes are particularly susceptible to genetic and environmental perturbation, we expect to develop a system useful for others who study oocyte biology and potential impacts that may cause their demise. Finally, we hope to generate a novel cell source for reprogramming of human somatic cells. This research is clearly aimed at a central issue of women's health as the formation, maintenance and demise of oocytes significantly impacts female physiology and health. The research is not eligible for federal funding as it relies heavily upon hESC lines that are excluded from federal funding and involves somatic cell nuclear transfer.
Renee Reijo Pera