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RISC-mediated control of selected chromatin regulators stabilizes ground state pluripotency of mouse embryonic stem cells
BACKGROUND: Embryonic stem cells are intrinsically unstable and differentiate spontaneously if they are not shielded from external stimuli. Although the nature of such instability is still controversial, growing evidence suggests that protein translation control may play a crucial role. RESULTS: We...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4858858/ https://www.ncbi.nlm.nih.gov/pubmed/27154007 http://dx.doi.org/10.1186/s13059-016-0952-x |
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author | Pandolfini, Luca Luzi, Ettore Bressan, Dario Ucciferri, Nadia Bertacchi, Michele Brandi, Rossella Rocchiccioli, Silvia D’Onofrio, Mara Cremisi, Federico |
author_facet | Pandolfini, Luca Luzi, Ettore Bressan, Dario Ucciferri, Nadia Bertacchi, Michele Brandi, Rossella Rocchiccioli, Silvia D’Onofrio, Mara Cremisi, Federico |
author_sort | Pandolfini, Luca |
collection | PubMed |
description | BACKGROUND: Embryonic stem cells are intrinsically unstable and differentiate spontaneously if they are not shielded from external stimuli. Although the nature of such instability is still controversial, growing evidence suggests that protein translation control may play a crucial role. RESULTS: We performed an integrated analysis of RNA and proteins at the transition between naïve embryonic stem cells and cells primed to differentiate. During this transition, mRNAs coding for chromatin regulators are specifically released from translational inhibition mediated by RNA-induced silencing complex (RISC). This suggests that, prior to differentiation, the propensity of embryonic stem cells to change their epigenetic status is hampered by RNA interference. The expression of these chromatin regulators is reinstated following acute inactivation of RISC and it correlates with loss of stemness markers and activation of early cell differentiation markers in treated embryonic stem cells. CONCLUSIONS: We propose that RISC-mediated inhibition of specific sets of chromatin regulators is a primary mechanism for preserving embryonic stem cell pluripotency while inhibiting the onset of embryonic developmental programs. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13059-016-0952-x) contains supplementary material, which is available to authorized users. |
format | Online Article Text |
id | pubmed-4858858 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-48588582016-05-07 RISC-mediated control of selected chromatin regulators stabilizes ground state pluripotency of mouse embryonic stem cells Pandolfini, Luca Luzi, Ettore Bressan, Dario Ucciferri, Nadia Bertacchi, Michele Brandi, Rossella Rocchiccioli, Silvia D’Onofrio, Mara Cremisi, Federico Genome Biol Research BACKGROUND: Embryonic stem cells are intrinsically unstable and differentiate spontaneously if they are not shielded from external stimuli. Although the nature of such instability is still controversial, growing evidence suggests that protein translation control may play a crucial role. RESULTS: We performed an integrated analysis of RNA and proteins at the transition between naïve embryonic stem cells and cells primed to differentiate. During this transition, mRNAs coding for chromatin regulators are specifically released from translational inhibition mediated by RNA-induced silencing complex (RISC). This suggests that, prior to differentiation, the propensity of embryonic stem cells to change their epigenetic status is hampered by RNA interference. The expression of these chromatin regulators is reinstated following acute inactivation of RISC and it correlates with loss of stemness markers and activation of early cell differentiation markers in treated embryonic stem cells. CONCLUSIONS: We propose that RISC-mediated inhibition of specific sets of chromatin regulators is a primary mechanism for preserving embryonic stem cell pluripotency while inhibiting the onset of embryonic developmental programs. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13059-016-0952-x) contains supplementary material, which is available to authorized users. BioMed Central 2016-05-06 /pmc/articles/PMC4858858/ /pubmed/27154007 http://dx.doi.org/10.1186/s13059-016-0952-x Text en © Pandolfini et al. 2016 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Research Pandolfini, Luca Luzi, Ettore Bressan, Dario Ucciferri, Nadia Bertacchi, Michele Brandi, Rossella Rocchiccioli, Silvia D’Onofrio, Mara Cremisi, Federico RISC-mediated control of selected chromatin regulators stabilizes ground state pluripotency of mouse embryonic stem cells |
title | RISC-mediated control of selected chromatin regulators stabilizes ground state pluripotency of mouse embryonic stem cells |
title_full | RISC-mediated control of selected chromatin regulators stabilizes ground state pluripotency of mouse embryonic stem cells |
title_fullStr | RISC-mediated control of selected chromatin regulators stabilizes ground state pluripotency of mouse embryonic stem cells |
title_full_unstemmed | RISC-mediated control of selected chromatin regulators stabilizes ground state pluripotency of mouse embryonic stem cells |
title_short | RISC-mediated control of selected chromatin regulators stabilizes ground state pluripotency of mouse embryonic stem cells |
title_sort | risc-mediated control of selected chromatin regulators stabilizes ground state pluripotency of mouse embryonic stem cells |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4858858/ https://www.ncbi.nlm.nih.gov/pubmed/27154007 http://dx.doi.org/10.1186/s13059-016-0952-x |
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