Molecular basis of cell fate plasticity - insights from the privileged cells

In the post-Yamanaka era, the rolling balls on Waddington's hilly landscape not only roll downward, but also go upward or sideways. This new-found mobility implies that the tantalizing somatic cell plasticity fueling regeneration, once only known to planarians and newts, might be sparking in the cells of mice and humans, if only we knew how to fully unlock it. The hope for ultimate regeneration was made even more tangible by the observations that partial reprogramming by the Yamanaka factors reverses many hallmarks of aging [76], even though the underlying mechanism remains unclear. We intend to revisit the milestones in the evolving understanding of cell fate plasticity and glean molecular insights from an unusual somatic cell state, the privileged cell state that reprograms in a manner defying the stochastic model. We synthesize our view of the molecular underpinning of cell fate plasticity, from which we speculate how to harness it for regeneration and rejuvenation. We propose that senescence, aging and malignancy represent distinct cell states with definable biochemical and biophysical parameters.