Characterization and germ line differentiation of non-rodent embryonic stem cells

点击翻译按钮获取中文摘要

The milk of transgenic dairy animals is a valuable source of complex recombinant, biopharmaceutical proteins that is safer and requires lower capital investment than traditional bioreactors. The current state of the art for generating transgenic farm animals is somatic cell nuclear transfer (SCNT), which is inefficient and expensive. Recently, we developed germ cell transplantation (GCT) as a novel, potentially more efficient alternative for the production of transgenic large animals. Availability of cell lines that can be modified and characterized before use for SCNT or GCT would substantially improve efficiency and commercial viability of transgenic animals for recombinant protein production. Objectives of this project are to derive stem cells from goat embryos and to study differentiation of these cells into male germ cells. The goat is of significant commercial interest for recombinant protein production. The goat also is an ideal large-animal model for studying germ lineage differentiation because embryogenesis, SCNT and embryo transfer are well understood, and we have developed transplantation assays for germ line differentiation in this species. We recently derived a goat embryonic stem cell line. Here, we will test the hypothesis that cell lines derived from goat embryos can differentiate into all tissue types of the body (a hallmark characteristic of embryonic stem cells). We will then use animal models developed by us to measure differentiation of embryo-derived stem cells to functional male germ cells that produce sperm. These studies will test the hypothesis that exposure to the testis environment will induce germ cell differentiation. Finally, we will test the hypothesis that stem cells present in the testis can revert to undifferentiated stem cells resembling those derived from the embryo. The expected impact of this project is to establish a large animal model for deriving functional male germ cells from embryonic stem cells. Availability of embryo- or germ cell derived stem cells is expected to translate into more efficient ways to generate transgenic large animals for large scale production of recombinant proteins. Importantly, this program will provide an ideal training environment for highly qualified individuals for academia and biotech industry.