Abstract
SummaryPluripotency is generated naturally during mammalian development through formation of the epiblast, founder tissue of the embryo proper. Pluripotency can be recreated by somatic cell reprogramming. Here we present evidence that the homeodomain protein Nanog mediates acquisition of both embryonic and induced pluripotency. Production of pluripotent hybrids by cell fusion is promoted by and dependent on Nanog. In transcription factor-induced molecular reprogramming, Nanog is initially dispensable but becomes essential for dedifferentiated intermediates to transit to ground state pluripotency. In the embryo, Nanog specifically demarcates the nascent epiblast, coincident with the domain of X chromosome reprogramming. Without Nanog, pluripotency does not develop, and the inner cell mass is trapped in a pre-pluripotent, indeterminate state that is ultimately nonviable. These findings suggest that Nanog choreographs synthesis of the naive epiblast ground state in the embryo and that this function is recapitulated in the culmination of somatic cell reprogramming.
Highlights
Pluripotency is the capacity of a single cell to generate in a flexible manner all cell lineages of the developing and adult organism
We investigated whether upregulation of endogenous Nanog may have a similar effect
Rex1, a sensitive indicator of undifferentiated embryonic stem (ES) cell status (Toyooka et al, 2008), is unchanged suggesting that the increase in Nanog is not secondary to reduced differentiation
Summary
Pluripotency is the capacity of a single cell to generate in a flexible manner all cell lineages of the developing and adult organism. This is an essential, albeit transient, attribute of cells in embryos that undergo regulative development. Mammalian zygotes follow a program of cleavage divisions and elaborate two extraembryonic lineages, trophoblast and hypoblast (Selwood and Johnson, 2006) This preparatory phase of development culminates in creation of the embryo founder tissue, a population of unrestricted pluripotent cells known as the epiblast (Gardner and Beddington, 1988; Nichols and Smith, 2009). Understanding of how pluripotent cells are generated remains rudimentary,
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