Due to its ethical acceptability and technical feasibility, production of induced pluripotent stem (iPS) cells from differentiated somatic cells by exogenous expression of several key transcription factors has given great promise to regenerative medicine and drug discovery 1. The most commonly used transcription factors in iPS cell induction are Oct4, Sox2, Klf4 and c-Myc 2. However, as c-Myc is a proto-oncogene that causes many kinds of malignant tumors, whether it is safe to be used as an iPS cell induction factor has long been a concern. Previous studies have successfully produced iPS cells without using c-Myc, and obtained viable chimera mice with reduced tumorigenicity 3. However, these three-factor-induced iPS cells had dramatically reduced induction efficiency and kinetics, and whether they could support full-term development of mice through tetraploid complementation remains unknown 4.

Compared with the induction system using “Yamanaka factors” with c-Myc in previous reports (24.04% ± 7.6%,) 6, the three-factor method had a slightly lower reprogramming efficiency when cells were cultured in the same KOSR medium. The pace of reprogramming also slowed down in the three-factor system, in which the GFP-positive clones were first observed around day 14 post infection, whereas the same process only took 8 to 10 days in the four-factor system.

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