A Heterogeneous Expression Pattern for Nanog in Embryonic Stem Cells
Article first published online: 5 JUL 2007
Copyright © 2007 AlphaMed Press
Volume 25, Issue 10, pages 2534–2542, October 2007
How to Cite
Singh, A. M., Hamazaki, T., Hankowski, K. E. and Terada, N. (2007), A Heterogeneous Expression Pattern for Nanog in Embryonic Stem Cells. STEM CELLS, 25: 2534–2542. doi: 10.1634/stemcells.2007-0126
- Issue published online: 2 JAN 2009
- Article first published online: 5 JUL 2007
- Manuscript Accepted: 23 JUN 2007
- Manuscript Received: 14 FEB 2007
- Embryonic stem cells;
- Primitive endoderm
Nanog is a critical homeodomain factor responsible for maintaining embryonic stem (ES) cell self-renewal and pluripotency. Of interest, Nanog expression is not homogeneous in the conventional culture of murine ES cells. A Nanog-high population expresses markers for pluripotent ES cells, whereas a Nanog-low population expresses markers for primitive endoderm, such as Gata6. Since the inner cell mass of early blastocysts has recently been reported to be heterogeneous in terms of Nanog and Gata6 expression, ES cells appear to closely resemble the developing stage from which they originate. We further demonstrate that Nanog can directly repress Gata6 expression through its binding to the proximal promoter region of the Gata6 gene and that overexpression of Nanog reduces heterogeneity during ES cell maintenance. Interestingly, Nanog heterogeneity does not correlate with the heterogeneous expression of stage-specific embryonic antigen-1, suggesting that multiple but overlapping levels of heterogeneity may exist in ES cells. These findings provide insight into the factors that control ES cell self-renewal and the earliest lineage commitment to primitive endoderm while also suggesting methods to promote homogeneity during ES cell maintenance.
Disclosure of potential conflicts of interest is found at the end of this article.