SCIENCE: 12. 10. 2012

Reprogrammed Cells Earn Biologists Top Honor

"The assumption that a cell's differentiation and maturation could not be reversed was first upended by work showing that a nucleus from a mature, specialized cell could be made to restart development as if it were young and later by other work showing that adding a few genes to mature cells in a laboratory dish could prompt them to behave like cells in early embryos. The two results netted John Gurdon of the University of Cambridge and Shinya Yamanaka of Kyoto University in Japan and the University of California, San Francisco, this year's Nobel Prize in physiology or medicine. The pair's work "revolutionised our understanding of how cells and organisms develop," the Nobel committee wrote in its award announcement."

http://www.sciencemag.org/content/338/6104/178.summary

The Developmental Capacity of Nuclei taken from Intestinal Epithelium Cells of Feeding Tadpoles

J. B. Gurdon

An important problem in embryology is whether the differentiation of cells depends upon a stable restriction of the genetic information contained in their nuclei. The technique of nuclear transplantation has shown to what extent the nuclei of differentiating cells can promote the formation of different cell types (e.g. King & Briggs, 1956; Gurdon, 1960c). Yet no experiments have so far been published on the transplantation of nuclei from fully differentiated normal cells. This is partly because it is difficult to obtain meaningful results from such experiments. The small amount of cytoplasm in differentiated cells renders their nuclei susceptible to damage through exposure to the saline medium, and this makes it difficult to assess the significance of the abnormalities resulting from their transplantation. It is, however, very desirable to know the developmental capacity of such nuclei, since any nuclear changes which are necessarily involved in cellular differentiation must have already taken place in cells of this kind.

http://dev.biologists.org/content/10/4/622.abstract

Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors.

Takahashi Kazutoshi, Yamanaka Shinya

"Differentiated cells can be reprogrammed to an embryonic-like state by transfer of nuclear contents into oocytes or by fusion with embryonic stem (ES) cells. Little is known about factors that induce this reprogramming. Here, we demonstrate induction of pluripotent stem cells from mouse embryonic or adult fibroblasts by introducing four factors, Oct3/4, Sox2, c-Myc, and Klf4, under ES cell culture conditions. Unexpectedly, Nanog was dispensable. These cells, which we designated iPS (induced pluripotent stem) cells, exhibit the morphology and growth properties of ES cells and express ES cell marker genes. Subcutaneous transplantation of iPS cells into nude mice resulted in tumors containing a variety of tissues from all three germ layers. Following injection into blastocysts, iPS cells contributed to mouse embryonic development. These data demonstrate that pluripotent stem cells can be directly generated from fibroblast cultures by the addition of only a few defined factors."

http://www.ncbi.nlm.nih.gov/pubmed/16904174