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EMBRYONIC STEM CELLS

A Heterogeneous Expression Pattern for Nanog in Embryonic Stem Cells

Department of Pathology, University of Florida College of Medicine, Gainesville, Florida, USA

Key Words. Embryonic stem cells • Nanog • Gata6 • Heterogeneity • Primitive endoderm

Correspondence: Naohiro Terada, M.D., Ph.D., Department of Pathology, University of Florida College of Medicine, Box 100275, Gainesville, Florida 32610, USA. Telephone: (352) 392-2696; Fax: (352) 392-6249; e-mail: terada{at}pathology.ufl.edu

Received February 14, 2007; accepted for publication June 23, 2007.
First published online in STEM CELLS EXPRESS   July 5, 2007.



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.