Somatic cell reprogramming by nuclear transplantation

点击翻译按钮获取中文摘要

Somatic cell nuclear transfer (SCNT) into enucleated oocytes has outstanding applications in research to study different cellular processes, as well as practical applications for cloning animals (e.g., save endangered species, replicate genetically superior animals, produce genetically modified animals, create animal models for medical research). Although more than 20 different species of animals have been cloned from somatic cells, the efficiency remains low and it is still not well understood what determines either successful development or failure in embryos created by SCNT. Because of a number of reasons that includes anatomical, physiological and metabolic similarities with humans, there is interest in the application of SCNT for the production of transgenic pigs to be used as models in biomedical research to study a variety of conditions. Therefore, it is important to gain a better understanding of the causes that limit the cloning success and then use the information obtained from these studies to establish novel strategies for increasing cloning efficiency. The major focus of this research program is on the preservation of the functional integrity of both the transplanted genome and recipient host cell in the production of fully viable SCNT embryos. Our studies will provide new insights on the potential effect of DNA damage on embryos produced in vitro, which will help on defining better conditions and safer protocols for in vitro embryo production. This is relevant because in vitro embryo production is used extensively not only in animals and but also in humans (e.g., the 2010 Nobel Prize was awarded for studies on in vitro fertilization). Our proposed studies will provide new valuable markers for more reliable selection of nuclear donor cells (to increase the efficiency of cloning), for the screening of culture conditions that minimize DNA damage (to produce healthier embryos in vitro), and for defining new and improved strategies to enhance chromatin reprogramming (to increase the efficiency of animal cloning from SCNT).