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Innovation in the Development of Induced Pluripotent Stem Cells

Presently, induced pluripotent stem cells (iPS) are created by introducing four defined genes to an adult cell. The genes reprogram the adult cell into a stem cell, which can differentiate into many different types of the cells in the body. Typically, the four genes introduced are Oct4, Sox2, Klf4 and c-Myc, a combination known as OSKM.   The challenge with the existing method has been that very few cells actually become iPS cells during reprogramming; as well;, because some of the reprogramming genes introduced are oncogenes, the risk of developing tumors grows.  Hiroyuki Hirai, from the University of Minnesota Medical School (Minnesota, USA), and colleagues fused two proteins – a master stem cell regulator (Oct4) and a fragment of a muscle cell inducer (MyoD) – to successfully power up the stem cell regulator, which can dramatically improve the efficiency and purity of reprogrammed iPS cells. Consequently, the team has developed a new gene model, called M3O-SKM, that improves iPS development by increasing efficiency, increasing purity, facilitating the reprogramming, decreasing the potential for tumor formation. and simplifying the process. The team submits that their finding has “far-reaching implications as a powerful tool for transcriptional reprogramming beyond application to [induced pluripotent stem cells] technology.”

Hirai, Hiroyuki; Tani, Tetsuya; Katoku-Kikyo, Nobuko; Kellner, Steven; Karian, Peter; Firpo, Meri; Kikyo, Nobuaki. “Radical Acceleration of Nuclear Reprogramming by Chromatin Remodeling With the Transactivation Domain of MyoD.” Stem Cells, July 5, 2011.

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