Mammalian development requires the specification of over 200 cell types from a single totipotent cell.

Extracellular signals and second messengers modulate cell-autonomous regulators such as OCT4, SOX2 and Nanog in a combinatorial complexity.

Knowledge of this circuitry might reveal how to achieve phenotypic changes without the genetic manipulation of OCT4, Nanog and other toti/pluripotency-associated genes.

The differentiation of embryonic stem (ES) cells is accompanied by activation and/or silencing of specific loci and global chromatin reorganization. Hyperdynamic association between the chromatin and the major proteins that determine its architecture is a hallmark of pluripotency, and that it is required for differentiation to occur.

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