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PMID: 19703398 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Nanog is the gateway to the pluripotent ground state.

Cell ·Vol. 138 ·No. 4 ·2009-08-21 ·Pages 722-37

Silva J, Nichols J, Theunissen TW, Guo G, van Oosten AL, Barrandon O, Wray J, Yamanaka S, Chambers I, Smith A

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.

MeSH Terms
Adult Stem Cells/cytology Animals Blastocyst/cytology Cell Dedifferentiation Cellular Reprogramming Embryonic Stem Cells/cytology Female Germ Layers/cytology Homeodomain Proteins/genetics,metabolism Mice Nanog Homeobox Protein X Chromosome/metabolism
Chemicals
Homeodomain Proteins Nanog Homeobox Protein Nanog protein, mouse
Authors & Affiliations
10 authors, click to expand affiliations / ORCID
Silva Jose
Wellcome Trust Centre for Stem Cell Research, University of Cambridge, Cambridge CB2 1QR, UK. jcs64@cscr.cam.ac.uk
Nichols Jennifer
Theunissen Thorold W
Guo Ge
van Oosten Anouk L
Barrandon Ornella
Wray Jason
Yamanaka Shinya
Chambers Ian
Smith Austin
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Article Info
Journal
Cell
Abbr.
Cell
ISSN
1097-4172
DOI
10.1016/j.cell.2009.07.039
Email
jcs64@cscr.cam.ac.uk
Published
2009-08-21
Pages
722-37
Language
English
Region
United States
NLM ID
0413066
PMCID
PMC3437554
Subset
IM
Grants
Medical Research Council · G0700665 · United Kingdom
Medical Research Council · G9806702 · United Kingdom
Wellcome Trust · United Kingdom
Biotechnology and Biological Sciences Research Council · United Kingdom
External Links
PubMed source DOI: 10.1016/j.cell.2009.07.039 PMC Full Text View journal details
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