Toti-/pluripotential stem cells and epigenetic modifications.
Nuclear reprogramming induces global changes of epigenetic profile and confers pluripotency on specialized somatic nuclei. Embryonic stem (ES) cells retain nuclear reprogramming activity as shown by cell fusion with adult somatic cells. The reprogrammed somatic nuclei resemble ES cell nuclei in pluripotential competence. Changes of histone tail modifications in somatic cell-derived genome by cell fusion demonstrate that the molecular process of nuclear reprogramming is separable at least in two steps: erasure of somatic epigenetic modification (genome-wide reprogramming) and establishment of pluripotential epigenetic modification (gene-specific reprogramming). In the latter step, the newly identified transcriptional factor Nanog functions in maintaining pluripotency in cooperation with other key gene Oct4. Somatic-derived Nanog is reactivated in the reprogrammed nuclei in hybrid cells and also in cloned blastocysts. It is unclear which key molecules are responsible for the nuclear reprogramming. It is, however, evident that adult somatic cell nuclei are capable of being reprogrammed in vitro by cell fusion with ES cells. A technological innovation for eliminating ES-derived chromosomes from the hybrid nuclei could make the production of personalized pluripotential stem cells without the need for therapeutic cloning possible.
Tada
Takashi
T
Stem Cell Engineering, Institute for Frontier Medical Sciences, Kyoto University, Kyoto, Japan. ttada@frontier.kyoto-u.ac.jp
D000818:Animals; D002459:Cell Fusion; D002467:Cell Nucleus / Q000502:physiology*; D004268:DNA-Binding Proteins / Q000502:physiology; D044127:Epigenesis, Genetic / Q000502:physiology*; D018398:Homeodomain Proteins / Q000502:physiology; D006801:Humans; D000071317:Nanog Homeobox Protein; D039904:Pluripotent Stem Cells / Q000502:physiology*
D004268:DNA-Binding Proteins; D018398:Homeodomain Proteins; C486780:NANOG protein, human; D000071317:Nanog Homeobox Protein; C475540:Nanog protein, mouse