Nanog Is the Gateway to the Pluripotent Ground State

By José C. R. Silva, Jennifer Nichols, T. Theunissen, G. Guo, A. V. van Oosten, Ornella Barrandon, Jason Wray, S. Yamanaka, Ian Chambers, Austin G Smith. Cell, 2009

1,117 citations recorded by the source corpus.

Summary 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.

Subfields: Genetics, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/d9d879cc1766f0d0a984177280845f6833bbc509

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Genetics

In Molecular Biology

Citations in the corpus

Resolution of cell fate decisions revealed by single-cell gene expression analysis from zygote to blastocyst. (2010, background): “In addition to the downregulation of Fgfr2 , cells expressing Sox2 earlier would be in a position to replenish depleting levels of maternal Sox2, thus maintaining the expression of key pluripotency Sox2 target genes such as Nanog (Rodda et al., 2005; Silva et al., 2009).”
Induced pluripotency: history, mechanisms, and applications. (2010, background): “The binding of pluripotency factors to their target genes might be facilitated by nucleosome remodelers such as Chd1 (Gaspar-Maia et al. 2009) and BAF (Singhal et al. 2010), both of which increase reprogramming efficiencies and kinetics when overexpressed.”
Somatic cell reprogramming and transitions between pluripotent states: facts, hypotheses, unresolved issues (2010, positive): “However, Nanog isalsoexpressed later inasubsetof innercellmasscellsand cooperates with other factors in X chromosome reactivation (Silva et al., 2009).”
Single-cell expression analyses during cellular reprogramming reveal an early stochastic and a late hierarchic phase. (2012, background): “locus (GFP cells), suggesting that the activation of the endogenous Nanog locus marks events that drive the cells to pluripotency (Silva et al., 2009).”
Senescence impairs successful reprogramming to pluripotent stem cells. (2009, background): “However this is a late event in reprogramming (Silva et al., 2009).”
Systematic Identification of Culture Conditions for Induction and Maintenance of Naive Human Pluripotency (2014, neutral): “EpiSCs can be converted to naive pluripotency by combined chemical and genetic manipulation (Guo et al., 2009; Hanna et al., 2009; Silva et al., 2009).”
Direct cell reprogramming is a stochastic process amenable to acceleration (2009, background): “31 Silva, J. et al., Nanog is the gateway to the pluripotent ground state. Cell 138 (4), 722-737 (2009).”
Resetting Transcription Factor Control Circuitry toward Ground-State Pluripotency in Human (2014, positive): “Expression of Nanog or Klf2 converts mouse EpiSC to groundstate ESC in 2iL (Hall et al., 2009; Silva et al., 2009).”
Suppression of Erk signalling promotes ground state pluripotency in the mouse embryo (2009, background): “The relationship between pluripotent cells that exist transiently in the mammalian embryo and immortal ES cells in culture has not been fully defined (Gardner and Brook, 1997; Smith, 2001).”
Dedifferentiation, transdifferentiation and reprogramming: three routes to regeneration (2011, background): “During development, NANOG is expressed by the pluripotent cells of the inner cell mass (ICM) and, accordingly, embryos that lack this gene fail to develop the IC”
Control of Embryonic Stem Cell State (2011, background): “…et al., 2007), Nanog promotes a stable undifferentiated ESC state (Chambers et al., 2007), is necessary for pluripotency to develop in ICM cells (Silva et al., 2009), and co-occupies most sites with Oct4 and Sox2 throughout the ESC genome (Marson et al., 2008b), so it is included here as a…”
A Small Molecule Inhibitor of Tgf-β Signaling Replaces Sox2 in Reprogramming by Inducing Nanog (2009, background): “Unlike previously described partially reprogrammed cells (Mikkelsen et al., 2008; Silva et al., 2009), the RepSox-responsive intermediates could not be reprogrammed with AZA or 2i treatment, suggesting that they are distinct.”