Laboratory for Genomic Reprogramming
Team Leader
Teruhiko WAKAYAMA (Ph.D.)
Cloning mammals by nuclear transfer began over fifteen years ago, yet the basic biology underlying this process remains unclear. We have succeeded in generating cloned mice from adult/fetus somatic and cultured (e.g., ES) cells. As in other mammals, the overall efficiency of mouse cloning in all reports is less than 5%. Why is this efficiency so low? Perhaps only a small percentage of cells in any given population are "cloning-competent" or because of technical problems (e.g., nuclear damage), but there exists a bewildering range of other possibilities. The concept of "nuclear reprogramming" links the efficiency of cloning to changes that an incoming nucleus must undergo to direct development, but its mechanisms are unknown. We have derived ES cell lines via nuclear transfer (ntES cell lines) from adult mouse somatic cells (e.g., tail-tip fibroblasts). ntES cells contribute to an extensive variety of cell types, including germ cells in vivo, suggesting that they have been effectively reprogrammed and are fully pluripotent. Thus, we now have a uniquely powerful research model to investigate the biology of mammalian cloning, including the mechanisms that underlie reprogramming. This is expected to provide insights that will allow us to increase cloning efficiency significantly.
- Improvement of nuclear transfer techniques
- Study of genomic reprogramming in mouse oocytes cytoplasm
- Comparison with ntES cell line and ES cell line
- August 25, 2009
- Evidence that earth's gravity is indispensable for normal mammalian embryo genesis
- August 25, 2009
- Embryos feel gravity's pull
- November 04, 2008
- Clones from dead, frozen mice
- February 20, 2007
- New source of oocytes for SCNT?
- November 13, 2009
- Embryonic development-lost in space?
Experiments simulating zero-gravity conditions reveal developmental difficulties arising from mammalian reproduction in space
- November 14, 2008
- Cloning: Back from the ice
RIKEN researchers have produced healthy cloned mice from cells taken from bodies frozen for 16 years
- June 08,2007
- When bad eggs are good
Eggs that fail to become fertilized can be used to obtain embryonic stem cells
- December 15, 2006
- Deft hands enable cloning
- Li C, Mizutani E, Ono T and Wakayama T.:
"An Efficient Method for Generating Transgenic Mice Using NaOH-Treated Spermatozoa."
Biol Reprod. 82: 331-340 (2010) - Ono T, Mizutani E, Chong L, and Wakayama T.:
"Preservation of sperm within the mouse cauda epididymidis in salt or sugars at room temperature."
Zygote 18: 245-256 (2010) - Dahl JA, Reiner AH, Klungland A, Wakayama T, and Collas P.:
"Histone H3 lysine 27 methylation asymmetry on developmentally-regulated promoters distinguish the first two lineages in mouse preimplantation embryos. "
PLoS One. 5 e9150 (2010) - Bui H.T, Wakayama S, Kishigami S, Kim HJ, Van Thuan N, and Wakayama T.:
"Effect of Trichostatin A on chromatin remodeling, histone modifications, DNA replication and transcriptional activity in cloned mouse embryos. "
Biol Reprod. 83: 454-463 (2010) - Hikichi T, Ohta H, Wakayama S, and Wakayama T.:
"Functional full-term placentas formed from parthenogenetic embryos using serial nuclear transfer. "
Development 137: 2841-2847 (2010) - Yamagata K, Ueda J, Mizutani E, Saitou M, and Wakayama T.:
"Survival and death of epiblast cells during embryonic stem cell derivation revealed by long-term live-cell imaging with an Oct4 reporter system."
Dev Biol. 346: 90-101 (2010) - Ono T, Li C, Mizutani E, Terashita Y, Yamagata K, and Wakayama T.:
"Inhibition of Class IIb Histone Deacetylase Significantly Improves Cloning Efficiency in Mice"
Biol Reprod. 83: 929-937 (2010) - Kim HR, Han RX, Wakayama T, Park CS, and Jin DI.:
"Aberrant protein expression in the placenta of cloned mouse derived from embryonic stem cell."
Placenta 31: 853-859 (2010) - Bui HT, Wakayama S, Mizutani E, Park KK, Kim JH, Van Thuan N, and Wakayama T.:
"Essential role of paternal chromatin in the regulation of transcriptional activity during mouse preimplantation development."
Reproduction 141: 67-77 (2011) - Hirata S, Fukasawa H, Wakayama S, Wakayama T, and Hoshi K.:
"Generation of Healthy Cloned Mice using Enucleated Cryopreserved Oocytes."
Cellular Reprogramming 13: 7-11 (2011)