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

Pereira, Carlos F. LU ; Piccolo, Francesco M.; Tsubouchi, Tomomi; Sauer, Stephan P A; Ryan, Natalie K.; Bruno, Ludovica; Landeira, David; Santos, Joana; Banito, Ana and Gil, Jesus, et al. (2010) In Cell Stem Cell 6(6). p.547-556
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... (More)

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.

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published
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Cell Stem Cell
volume
6
issue
6
pages
10 pages
publisher
Cell Press
external identifiers
  • scopus:77953086963
ISSN
1934-5909
DOI
10.1016/j.stem.2010.04.013
language
English
LU publication?
no
id
2ccf8114-2505-4801-921a-ff5d55b388ad
date added to LUP
2017-10-02 17:30:51
date last changed
2018-05-29 10:18:54
@article{2ccf8114-2505-4801-921a-ff5d55b388ad,
  abstract     = {<p>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.</p>},
  author       = {Pereira, Carlos F. and Piccolo, Francesco M. and Tsubouchi, Tomomi and Sauer, Stephan P A and Ryan, Natalie K. and Bruno, Ludovica and Landeira, David and Santos, Joana and Banito, Ana and Gil, Jesus and Koseki, Haruhiko and Merkenschlager, Matthias and Fisher, Amanda G.},
  issn         = {1934-5909},
  language     = {eng},
  month        = {06},
  number       = {6},
  pages        = {547--556},
  publisher    = {Cell Press},
  series       = {Cell Stem Cell},
  title        = {ESCs require PRC2 to direct the successful reprogramming of differentiated cells toward pluripotency},
  url          = {http://dx.doi.org/10.1016/j.stem.2010.04.013},
  volume       = {6},
  year         = {2010},
}