Highly efficient generation of induced pluripotent stem cells from human keratinocytes

The generation of induced pluripotent stem (iPS) cells 1-4 has spawned unprecedented opportunities for investigating the molecular logic that underlies cellular pluripotency and reprogramming, as well as for obtaining patient-specific cells for future clinical applications. However, both prospects are hampered by the low efficiency of the reprogramming process. Here, we show that juvenile human primary keratinocytes can be efficiently reprogrammed to pluripotency by retroviral transduction with Oct4, Sox2, Klf4 and c-Myc. Keratinocyte-derived iPS (KiPS) cells appear indistinguishable from human embryonic stem (hES) cells in colony morphology, growth properties, expression of pluripotency-associated transcription factors and surface markers, as well as in vitro and in vivo differentiation potential. Notably, keratinocyte reprogramming to pluripotency is, at least, 100-fold more efficient and 2-fold faster than that of fibroblasts. This increase in reprogramming efficiency allowed us to expand the practicability of the technology and to generate KiPS cells from single plucked hairs from adult individuals.

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Aasen T, Raya A, Barrero MJ, Garreta E, Consiglio A, Gonzalez F, Vassena R, Bilić J, Pekarik V, Tiscornia G, Edel M, Boué S, Izpisúa Belmonte JC