Laboratories
Laboratory for Genomic Reprogramming
Teruhiko WAKAYAMA
Team Leader
Teruhiko WAKAYAMA (Ph.D.)
mail

Research Areas

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.

Research Subject

  1. Improvement of nuclear transfer techniques
  2. Study of genomic reprogramming in mouse oocytes cytoplasm
  3. Comparison with ntES cell line and ES cell line

Related links

  1. RIKEN Center for Developmental Biology Website_Laboratories PageNew Window
  2. Individual Website Laboratory PageNew Window

Press release

August 25, 2009
Evidence that earth's gravity is indispensable for normal mammalian embryo genesis

RIKEN RESEARCH

November 13, 2009
Embryonic development-lost in space?
Experiments simulating zero-gravity conditions reveal developmental difficulties arising from mammalian reproduction in spaceNew Window
November 14, 2008
Cloning: Back from the ice
RIKEN researchers have produced healthy cloned mice from cells taken from bodies frozen for 16 yearsNew Window
June 08,2007
When bad eggs are good
Eggs that fail to become fertilized can be used to obtain embryonic stem cells New Window
December 15, 2006
Deft hands enable cloning New Window

List of Selected Publications

  1. 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)
  2. 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)
  3. 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)
  4. 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)
  5. 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)
  6. Ono T, Mizutani E, Li C, Yamagata K, and Wakayama T.:
    "Offspring from intracytoplasmic sperm injection of aged mouse oocytes treated with caffeine or MG132."
    Genesis. 49: 460-471 (2011)
  7. Terashita Y, Li C, Yamagata K, Sato E, and Wakayama T.:
    "Effect of Fluorescent Mercury Light Irradiation on In Vitro and In Vivo Development of Mouse Oocytes after Parthenogenetic Activation or Sperm Microinjection."
    J. Reprod. Dev. 57: 564-571 (2011)
  8. Li C, Mizutani E, Ono T, Terashita Y, Jia XF, Shi HJ, and Wakayama T.:
    "Intracytoplasmic Sperm Injection with Mouse Spermatozoa Preserved Without Freezing for Six Months Can Lead to Full-Term Development."
    Biol. Reprod. 85:1183-1190 (2011)
  9. Bui HT, Seo HJ, Park MR, Park JY, Van Thuan N, Wakayama T, and Kim JH.:
    "Histone Deacetylase Inhibition Improves Activation of Ribosomal RNA Genes and Embryonic Nucleolar Reprogramming in Cloned Mouse Embryos. "
    Biol. Reprod. 85: 1048-1056 (2011)
  10. Mizutani E, Yamagata K, Ono T, Akagi S, Geshi M, and Wakayama T.:
    "Abnormal chromosome segregation at early cleavage is a major cause of the full-term developmental failure of mouse clones."
    Dev. Biol., in press (2012)

Members

Principal Investigator

Teruhiko WAKAYAMA
Team Leader

Members

Sayaka WAKAYAMA
Research Scientist
Chong LI
Research Scientist
Kaori YAMANAKA
Technical Staff I
Yuko SAKAIDE
Technical Staff II