Genomic Reprogramming

Secret of the Clone

Unshakeable persistence and insatiable curiosity are key to the study of reproductive biology and genomic reprogramming, as Teruhiko Wakayama knows well; indeed, he has succeeded at what many had once thought impossible. As a postdoctoral fellow, he gained attention worldwide for his role in developing the first technique for cloning mice. Using this method, Wakayama was the first to produce multiple generations of genetically identical mice. And using a similar technique, his team has also derived embryonic stem cell lines via nuclear transfer (ntES cell lines) from adult mouse somatic cells. Wakayama intends to put these studies to work in unraveling the secrets of cloning and the resetting of genetic states.

Aims

E To identify the reprogramming factors that allow the oocyte nucleus to achieve its totipotency
E To understand the hows and whys of oocyte reprogramming
E To contribute to regenerative medicine by generating medically useful somatic cell-derived ES cells

Teruhiko Wakayama Ph.D.
Teruhiko Wakayama Ph.D.
"Eggs are very beautiful and
mysterious; I never get tired
of watching them"
Cloning mammals by nuclear transfer has succeeded in many species, yet the basic biology underlying this process remains unclear. Wakayama succeeded in generating cloned mice from adult/fetal somatic and cultured (e.g., ES) cells. As with other mammals, however, the overall efficiency of mouse cloning in all reports is less than 5%. Why is this procedure so inefficient? It may be that only a small percentage of cells in any given population are "cloning-competent," or because of technical problems (e.g., nuclear damage), but there is a range of other possibilities as well. The concept of "nuclear reprogramming" links the efficiency of cloning to changes that an incoming nucleus must undergo to direct development, by mechanisms which have yet to be elucidated. Wakayama's lab has also derived ES cell lines via nuclear transfer (ntES cell lines) from adult mouse somatic cells (e.g., tail-tip fibroblasts). These ntES cells contribute to an extensive range of cell types, including germ cells, in vivo, suggesting that they have been effectively reprogrammed and are pluripotent. Using this powerful research model, Dr. Wakayama will investigate the biology of mammalian cloning, and the mechanisms that underlie reprogramming.


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