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EMBRYONIC STEM CELLS

Polycomb Repressive Complex 2 Is Dispensable for Maintenance of Embryonic Stem Cell Pluripotency

Department of Genetics and Carolina Center for Genome Sciences, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA

Key Words. Embryonic stem cell • Pluripotent • Epigenetics • Gene expression • Embryo

Correspondence: Terry Magnuson, Ph.D., Department of Genetics and Carolina Center for Genome Sciences, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA. Telephone: 919-843-6475; Fax: 919-843-4682; e-mail: trm4{at}med.unc.edu

Received February 18, 2008; accepted for publication March 19, 2008.
First published online in STEM CELLS EXPRESS   April 10, 2008.

Polycomb repressive complex 2 (PRC2) methylates histone H3 tails at lysine 27 and is essential for embryonic development. The three core components of PRC2, Eed, Ezh2, and Suz12, are also highly expressed in embryonic stem (ES) cells, where they are postulated to repress developmental regulators and thereby prevent differentiation to maintain the pluripotent state. We performed gene expression and chimera analyses on low- and high-passage Eed^null ES cells to determine whether PRC2 is required for the maintenance of pluripotency. We report here that although developmental regulators are overexpressed in Eed^null ES cells, both low- and high-passage cells are functionally pluripotent. We hypothesize that they are pluripotent because they maintain expression of critical pluripotency factors. Given that EED is required for stability of EZH2, the catalytic subunit of the complex, these data suggest that PRC2 is not necessary for the maintenance of the pluripotent state in ES cells. We propose a positive-only model of embryonic stem cell maintenance, where positive regulation of pluripotency factors is sufficient to mediate stem cell pluripotency.

Disclosure of potential conflicts of interest is found at the end of this article.

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