Riken-Led Team Finds Way to Improve iPS Production Efficiency 20 Times

Tokyo, Feb. 7 (Jiji Press)--A research team led by the Japanese government-backed Riken has discovered a novel way in mice to improve some 20 times the efficiency of the production of induced pluripotent stem (iPS) cells, according to an article published on the U.S. journal Cell Stem Cell. The team, also including researchers from the University of Tokyo, Kyushu University and the University of Tsukuba, focused on proteins called histones around which thread-like DNA is bound. According to the report on the scientific journal's Thursday edition, Riken's senior research fellow Shunsuke Ishii and full-time researcher Toshie Shinagawa discovered with their colleagues that fertilized and unfertilized eggs contain significant amounts of histone variants called TH2A and TH2B as testis cells do. Around the variants, DNA is bound far more loosely than around regular histones and activities to switch on genes are robust. Assuming TH2A and TH2B would work to enhance iPS cell production under the four-gene-injection method developed by Kyoto University Prof. Shinya Yamanaka, the team added genes to make the histone variants to the four genes. When the histone variants' genes worked, iPS cell generation from mouse fetal cells was enhanced ninefold, the team said in the article. In a further experiment, the researchers added another gene to produce protein called P-Npm and saw iPS cell output improve 18-fold, it noted. The introduction of the variants also helped make iPS cell production twice to three times as fast as under the Yamanaka method. The looseness of bound DNA is believed to have made it easier for Yamanaka's four genes to perform, the team said. This mechanism seems to work also when cloned embryos are made, according to Ishii. The mechanism is believed to play a key role in "reprogramming" skin, nerve, muscle and other mature cells back to a pluripotent state from which the cells develop into various tissue. In eggs, there are other proteins believed to be involved in cell reprogramming, Ishii said, hinting that the proteins are also likely to help improve the efficiency of iPS cell production. END