By Stuart P. Atkinson
Many questions surrounding induced pluripotent stem cells (iPSCs) still remain, including a definitive answer to the question of the origin of the cells which ultimately undergo reprogramming. Two models exist; the stochastic model which suggests that random cells from an initial culture will eventually become iPSCs, and the elite model, which posits that only a few cells from within a culture have the ability to become reprogrammed, hence the low relative efficiency of the reprogramming process. In the elite model, it is supposed that such cells may be tissue-specific stem/progenitor cells which might already express certain factors required for the reprogramming process. A recent study in Stem Cells from the lab of Rudolf Jaenisch (Kim et al), also reported on the Stem Cells Portal (Reprogramming of Postnatal Neurons into Induced Pluripotent Stem Cells by Defined Factors) suggested that a pure terminally differentiated population of cells could be reprogrammed with the expression of Oct4, Sox2, Klf4 and Myc (OSKM) but only with expression of Rest and under conditions of p53 inhibition, giving some credence towards the stochastic model. However, a study in PNAS from the lab of Mari Dezawa at the Tohoku University Graduate School of Medicine, Sendai, Japan, suggest that only a small sub-population of cells from a naïve dermal fibroblast culture which express stem cell-like properties can be reprogrammed (Wakao et al), thus instead supporting the elite model.