Stem Cell Pioneer Yamanaka Discovers New Factor, Glis1, For iPS Cell Production
Yamanaka and colleagues have discovered that a new transcription factor Glis1, enriched in unfertilized and recently fertilized eggs, could replace Myc to produce iPS cells.
AsianScientist (Jun. 9, 2011) - Japanese researchers have taken a step forward in developing more reliable stem cell technologies by discovering an efficient method to reprogram adult cells into stem cells that reduces the risk of stem cells transforming into cancer cells.
Ever since Shinya Yamanaka first reprogrammed mice and human adult cells into induced pluripotent stem cells (iPS cells) using a cocktail of four protein transcription factors, scientists have been attempting to develop new techniques to make iPS cell production safer and more high yielding. The first generation of four transcription factors included the cancer-inducing protein Myc, which led to the development of cancer in iPS cell-derived mice.
In a study published in yesterday's issue of Nature, Yamanaka and colleagues discovered that a new transcription factor Glis1, enriched in unfertilized and recently fertilized eggs, could replace Myc to produce iPS cells from adult cells with higher efficiency and decreased tumorigenicity.
The researchers performed a screen of over 1,400 different human transcription factors for their ability to produce iPS cells and discovered that Glis1 increased 10-fold the proportion of adult cells that transformed into iPS cells when compared to Myc.
To probe the mechanism behind Glis1-mediated iPS cell production, the scientists analyzed the cells using a DNA microarray and discovered that Glis1 promoted several pathways associated with reprogramming. Glis1 also suppressed the proliferation of defective partially reprogrammed cells.
The investigators also noted that mouse and human iPS cells developed using Glis1 in place of Myc showed similar characteristics to embryonic stem cells. Mouse iPS cells were also able to produce viable mice. Unlike mice produced from Myc-derived iPS cells, the mice produced from Glis1-derived iPS cells did not show a marked increase in mortality.
The authors conclude that the improved safety and efficiency of iPS cell production using Glis1 would be “beneficial for future applications of iPS cell technology.”
The article can be found at: Maekawa M et al. (2011) Direct reprogramming of somatic cells is promoted by maternal transcription factor Glis1.
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