ESCs require PRC2 to direct the successful reprogramming of differentiated cells toward pluripotency

Research output: Contribution to journalArticle

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.

Details

Authors
  • Carlos F. Pereira
  • Francesco M. Piccolo
  • Tomomi Tsubouchi
  • Stephan P A Sauer
  • Natalie K. Ryan
  • Ludovica Bruno
  • David Landeira
  • Joana Santos
  • Ana Banito
  • Jesus Gil
  • Haruhiko Koseki
  • Matthias Merkenschlager
  • Amanda G. Fisher
External organisations
  • Hammersmith Hospital
  • Riken Research Center for Allergy and Immunology
Original languageEnglish
Pages (from-to)547-556
Number of pages10
JournalCell Stem Cell
Volume6
Issue number6
StatePublished - 2010 Jun 4
Publication categoryResearch
Peer-reviewedYes
Externally publishedYes