1. ESCs require PRC2 to direct the successful reprogramming of differentiated cells toward pluripotency.
- Author
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Pereira CF, Piccolo FM, Tsubouchi T, Sauer S, Ryan NK, Bruno L, Landeira D, Santos J, Banito A, Gil J, Koseki H, Merkenschlager M, and Fisher AG
- Subjects
- Animals, Antigens, Differentiation biosynthesis, Antigens, Differentiation genetics, B-Lymphocytes pathology, Cell Fusion, Cell Line, Transformed, Cellular Reprogramming genetics, Embryonic Stem Cells pathology, Gene Knockout Techniques, Histone-Lysine N-Methyltransferase genetics, Humans, Induced Pluripotent Stem Cells pathology, Mice, Neoplastic Stem Cells pathology, Polycomb Repressive Complex 2, Polycomb-Group Proteins, Repressor Proteins genetics, Telomerase biosynthesis, Telomerase genetics, Transcription Factors biosynthesis, Transcription Factors genetics, B-Lymphocytes metabolism, Embryonic Stem Cells metabolism, Histone-Lysine N-Methyltransferase metabolism, Induced Pluripotent Stem Cells metabolism, Neoplastic Stem Cells metabolism, Repressor Proteins metabolism
- Abstract
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., (Copyright 2010 Elsevier Inc. All rights reserved.)
- Published
- 2010
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