ESCs require PRC2 to direct the successful reprogramming of differentiated cells toward pluripotency.
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.
Pereira
Carlos F
CF
MRC Clinical Sciences Centre, Imperial College School of Medicine, Hammersmith Hospital, London, UK.
Piccolo
Francesco M
FM
Tsubouchi
Tomomi
T
Sauer
Stephan
S
Ryan
Natalie K
NK
Bruno
Ludovica
L
Landeira
David
D
Santos
Joana
J
Banito
Ana
A
Gil
Jesus
J
Koseki
Haruhiko
H
Merkenschlager
Matthias
M
Fisher
Amanda G
AG
D000818:Animals; D000943:Antigens, Differentiation / Q000096:biosynthesis / Q000235:genetics; D001402:B-Lymphocytes / Q000378:metabolism* / Q000473:pathology; D002459:Cell Fusion; D002461:Cell Line, Transformed; D065150:Cellular Reprogramming / Q000235:genetics; D053595:Embryonic Stem Cells / Q000378:metabolism* / Q000473:pathology; D055786:Gene Knockout Techniques; D011495:Histone-Lysine N-Methyltransferase / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D014411:Neoplastic Stem Cells / Q000378:metabolism* / Q000473:pathology; D063151:Polycomb Repressive Complex 2; D063146:Polycomb-Group Proteins; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D019098:Telomerase / Q000096:biosynthesis / Q000235:genetics; D014157:Transcription Factors / Q000096:biosynthesis / Q000235:genetics
D000943:Antigens, Differentiation; C107275:Eed protein, mouse; D063146:Polycomb-Group Proteins; D012097:Repressor Proteins; D014157:Transcription Factors; D011495:Histone-Lysine N-Methyltransferase; D063151:Polycomb Repressive Complex 2; C509186:TERT protein, human; D019098:Telomerase