Nanog Is the Gateway to the Pluripotent Ground State

Jose Silva, Jennifer Nichols, Thorold W. Theunissen, Ge Guo, Anouk L. van Oosten, Ornella Barrandon, Jason Wray, Shinya Yamanaka, Ian Chambers, Austin Smith

Research output: Contribution to journalArticlepeer-review

747 Scopus citations

Abstract

Pluripotency 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.

Original languageEnglish
Pages (from-to)722-737
Number of pages16
JournalCell
Volume138
Issue number4
DOIs
StatePublished - Aug 21 2009

Keywords

  • STEMCELL

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