Different strategies induce nuclear reprogramming towards pluripotency. (a) During reprogramming by nuclear transfer to eggs, the nucleus of a cell is transplanted into an unfertilised egg whose own nucleus has been removed [1]. The resulting embryos, larvae and adults have the same genetic constitution as the donor nucleus. The animal and vegetal poles of the egg are shown in brown and yellow, respectively. (b) For nuclear reprogramming by nuclear transfer to Xenopus oocytes, multiple mammalian nuclei are transplanted into the nucleus (germinal vesicle) of a meiotic prophase I oocyte [5]. Transcriptional reactivation of previously silenced genes is induced without cell division or DNA synthesis, and no new cell types are formed. The animal and vegetal poles of the oocyte are shown in brown and yellow, respectively. (c) The nuclei of distinct cell types can be induced to reside within a common cytoplasm [8]. The fused cells form heterokaryons, in which the nuclei remain as separate entities, and these can be maintained by inhibiting cell division. (d) Pluripotency can be induced in cultured somatic cells by overexpression of embryonic stem (ES) cell-specific transcription factors or by overexpression of small noncoding RNAs together with histone deacetylases inhibitors [11,58]. The cells obtained are very similar to ES cells. Adapted, with permission, from [14].