Figure 1

The black box of reprogramming. Despite the innovation of multiple methods to convert a somatic cell to a pluripotent phenotype over the past 50 years, the mechanisms remain largely unknown. Reprogramming methods: (1) Nuclear transfer: injection of a mammalian somatic cell nucleus into an enucleated oocyte will re-initiate the zygotic gene program in the transferred nucleus and permit embryonic development to the blastocyst stage (or later), from which pluripotent cells can be derived. (2) Cell fusion: after fusion of somatic cells with embryonic stem (ES) cells, the genetic program of the ES cell dominates in resulting heterokaryons, with pluripotent gene expression and epigenetic patterns evident in the somatic cell nucleus. (3) Direct reprogramming: introduction of defined transcription factors (e.g. OCT4, SOX2, KLF4, MYC) into somatic cells followed by selection under ES cell culture conditions yields induced pluripotent stem (iPS) cells, with morphological and functional features indistinguishable from blastocyst-derived ES cells.