Kinetic barriers in transdifferentiation.

Feature to: Jiang H. et al. Cell cycle and p53 gate the direct conversion of human fibroblasts to 2 The unidirectional and deterministic development of a zygote to trillions of cells that constitute a human produces the impression that it is an irreversible process, perhaps driven by reduction in free energy (G), as postulated in the Waddington Model, the prevailing doctrine in developmental biology. This model however, has great difficulties in explaining induced pluripotency 1 , where any somatic cells (with presumed low G) can be reprogrammed epigenetically to pluripotent stem cells (with presumed high G); nor the reestablishment of totipotency by the fusion of an egg and a sperm – two terminally differentiated cells. A first principle analysis suggests that epigenetic reprogramming is an isoenergetic process if we assume that epigenetic information of the original cell and the converted cell are similar. With no significant change in enthalpy and at constant temperature, G reflects changes in information content of the cell. As long as there is no significant change in the total epigenetic information content, there is no mythical cell type at the apex of energy landscape; it is largely flat. The