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Low efficiency of induced pluripotent stem (iPS) cell induction. Among fibroblasts expressing all four transgenes, less than 1% becomes iPS cells. The low efficiency may suggest that tissue stem cells co‐existing in fibroblast culture are the origin of iPS cells. Alternatively, the activation of additional genes by retroviral integration may be required. Another possible mechanism is that induction of iPS cells requires specific amounts and patterns of expression of the four factors.
