When new cell types are formed after reprogramming in nuclear transfer to eggs and in induced pluripotency experiments, extensive cell division always takes place before new cell types appear. It has been speculated that cell division might contribute to reprogramming, possibly through the replacement of chromosomal proteins at mitosis or by the assimilation of new chromosomal proteins during DNA synthesis [89]. However, reprogramming as judged by new gene transcription clearly does not require cell division or DNA synthesis, because these do not take place in oocyte nuclear transfer or in heterokaryon experiments [5,19,90]. It is also known that DNA demethylation can occur in the absence of cell division [9,43,91]. In another example, the conversion of C. elegans Y epithelial cells into motoneurons can occur in the absence of cell division [92]. Nevertheless, cell divisions seem to facilitate reprogramming in systems where they occur and may be required for a full level of transcription and for the generation of new cell types [93,94]. The resetting of replication origins from a somatic type to an embryonic one is seen when somatic nuclei are incubated in oocyte extract, suggesting that this is important for reprogramming by nuclear transfer [95,96].
