With the advent of nuclear-transfer cloning, it is now possible to produce mice from the nuclei of differentiated cells, such as peripheral blood lymphocytes and olfactory sensory neurons.
However, unlike most other clones, those formed with the nuclei of differentiated cells were generated by a two-step nuclear-transfer procedure that might allow the donor genome further reprogramming. Thus, these findings do not settle the question of whether the egg cytoplasm can itself reprogram a fully differentiated nucleus. It therefore remains a possibility that many cloned mammals might be derived from rare stem cells present in donor-cell samples rather than derived from differentiated cells themselves.
In a new study publishing in the June 21 issue of Current Biology, researchers at the RIKEN Bioresource Center and the RIKEN Research Center for Allergy and Immunology in Japan report the birth of offspring after direct nuclear transfer from natural killer T (NKT) cells, a unique lymphocyte cell population. The cloned pups, as well as their placentas, possess the rearranged T cell receptor (TCR) genomic loci that are specific for NKT cells, positively demonstrating that the cloned animals and their placentas were derived from fully differentiated cells. The results provide the evidence that terminally differentiated cell nuclei are competent to support the development of embryos as well as placentas after conventional, one-step nuclear transfer. The findings also necessitate a revision of prevailing ideas about the genomic plasticity of differentiated somatic cells.
The researchers include Kimiko Inoue, Narumi Ogonuki, Shinichi Noda, Hiroyuki Miyoshi, Hiromi Miki, and Atsuo Ogura of the RIKEN Bioresource Center; and Hiroshi Wakao, Ken-ichiro Seino, Rika Nambu-Wakao, Haruhiko Koseki, and Masaru Taniguchi of the RIKEN Research Center for Allergy and Immunology. This research was supported by grants from the Ministry of Education; the Ministry of Health, Labour, and Welfare; the Japan Science and Technology Agency; and the Human Science Foundation (all Japanese).