ESCs Require PRC2 to Direct the Successful Reprogramming of Differentiated Cells toward Pluripotency

• DOI: 10.1016/j.stem.2010.04.013
• Publication Date: 2010-06-04T08:46:58Z
• Authors: Carlos F. Pereira; Francesco M. Piccolo; Tomomi Tsubouchi; Stephan Sauer; Natalie K. Ryan; Ludovica Bruno; David Landeira; Joana Santos; Ana Banito; Jesus Gil; Haruhiko Koseki; Matthias Merkensc...; Amanda G. Fisher
• Keywords: 0301 basic medicine; B-Lymphocytes; Induced Pluripotent Stem Cells; Polycomb Repressive Complex 2; Polycomb-Group Proteins; Cell Biology; Histone-Lysine N-Methyltransferase; Cellular Reprogramming; STEMCELL; Antigens, Differentiation; Cell Fusion; Repressor Proteins; Gene Knockout Techniques; Mice; 03 medical and health sciences; Genetics; Neoplastic Stem Cells; Molecular Medicine; Animals; Humans; Telomerase; Embryonic Stem Cells; Cell Line, Transformed; Transcription Factors

Embryonic stem cells (ESCs) are pluripotent, self-renewing, and have the ability to reprogram differentiated cell types to pluripotency upon cellular fusion. Polycomb-group (PcG) proteins are important for restraining the inappropriate expression of lineage-specifying factors in ESCs. To investigate whether PcG proteins are required for establishing, rather than maintaining, the pluripotent state, we compared the ability of wild-type, PRC1-, and PRC2-depleted ESCs to reprogram human lymphocytes. We show that ESCs lacking either PRC1 or PRC2 are unable to successfully reprogram B cells toward pluripotency. This defect is a direct consequence of the lack of PcG activity because it could be efficiently rescued by reconstituting PRC2 activity in PRC2-deficient ESCs. Surprisingly, the failure of PRC2-deficient ESCs to reprogram somatic cells is functionally dominant, demonstrating a critical requirement for PcG proteins in the chromatin-remodeling events required for the direct conversion of differentiated cells toward pluripotency.