Generation of cloned mice by direct nuclear transfer from natural killer T cells.
Cloning mammals by nuclear transfer (NT) remains inefficient. One fundamental question is whether clones have really been derived from differentiated cells rather than from rare stem cells present in donor-cell samples. To date, cells, such as mature lymphocytes, with genetic differentiation markers have been cloned to generate mice only via a two-step NT involving embryonic stem (ES) cell generation and tetraploid complementation [1, 2 and 3]. Here, we show that the genome of a unique T-cell population, natural killer T (NKT) cells, can be fully reprogrammed by a single-step NT. The pups and their placentas possessed the rearranged TCR loci specific for NKT cells. The NKT-cell-cloned embryos had a high developmental potential in vitro: Most (71%) developed to the morula/blastocyst stage, in marked contrast to embryos from peripheral blood T cells (12%; p < 1 x 10(-25)). Furthermore, ES cell lines were efficiently established from these NKT-cell blastocysts. These findings clearly indicate a high level of plasticity in the NKT-cell genome. Thus, differentiation of the genome is not always a barrier to NT cloning for either reproductive or therapeutic purposes, so we can now postulate that at least some mammals cloned to date have indeed been derived from differentiated donor cells.
Inoue
Kimiko
K
RIKEN Bioresource Center, Tsukuba, Ibaraki 305-0074, Japan.
Wakao
Hiroshi
H
Ogonuki
Narumi
N
Miki
Hiromi
H
Seino
Ken-ichiro
K
Nambu-Wakao
Rika
R
Noda
Shinichi
S
Miyoshi
Hiroyuki
H
Koseki
Haruhiko
H
Taniguchi
Masaru
M
Ogura
Atsuo
A
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001755:Blastocyst / Q000502:physiology; D002467:Cell Nucleus / Q000235:genetics*; D019976:Cloning, Organism / Q000379:methods*; D047108:Embryonic Development / Q000235:genetics; D005260:Female; D018014:Gene Transfer Techniques; D007694:Killer Cells, Natural / Q000502:physiology*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D008969:Molecular Sequence Data; D011948:Receptors, Antigen, T-Cell / Q000235:genetics
D011948:Receptors, Antigen, T-Cell