June 14, 2011
Transcription factor Glis1 promotes the generation of safe iPS cells
A research group led by Shinya Yamanaka, director of Center for iPS Cell Research and Application, Kyoto University, has discovered that induced pluripotent stem (iPS) cells can be induced very efficiently compared to the conventional method, when transcription factor Glis1, which is strongly expressed in the unfertilized egg, is used. The study was conducted in collaboration with Naoki Goshima, a principal investigator at Biomedicinal Information Research Center, the National Institute of Advanced Industrial Science and Technology.
Originally, iPS cells are generated by introducing four transcription factors (Oct3/4, Sox2, Klf4, c-Myc) to mouse or human fibroblasts by retroviral vectors, but tumorigenesis caused by c-Myc proto-oncogene remains a major concern. In addition, as the generation efficiency is low if iPS cells are made with three factors, without c-Myc, it has been necessary to establish a method to efficiently induce safe iPS cells.
In this study, the group searched for new factors involved in the induction of iPS cells and identified several factors. Of those, when Glis1 was induced to mouse or human fibroblasts along with three factors (Oct3/4, Sox2, Klf4) via retroviral vectors, the efficiency of iPS cell generation significantly improved in all cases. In addition, it was found that Glis1 inhibits the proliferation of cells with imperfect reprogramming but only proliferates completely reprogrammed ones. When the researchers performed a detailed analysis on the mechanism of Glis1, they found that Glis1 was able to facilitate reprogramming by increasing the expressions of several genes that are reported to be involved in reprogramming.
These results demonstrate the possibility that iPS cells can be efficiently established with high safety by using Glis1. It is hoped that the findings will significantly contribute to the establishment of a method for generating iPS cells that can be used in clinical applications.
"Direct reprogramming of somatic cells is promoted by maternal transcription factor Glis1"
Momoko Maekawa, Kei Yamaguchi, Tomonori Nakamura, Ran Shibukawa, Ikumi Kodanaka, Tomoko Ichisaka, Yoshifumi Kawamura, Hiromi Mochizuki, Naoki Goshima, and Shinya Yamanaka
Nature, Volume: 474, Pages: 225-229, Date published: 09 June 2011, DOI: 10.1038/nature10106