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Genome Biol. 2016 May 6;17(1):94. doi: 10.1186/s13059-016-0952-x.

RISC-mediated control of selected chromatin regulators stabilizes ground state pluripotency of mouse embryonic stem cells.

Author information

1
Scuola Normale Superiore of Pisa, Piazza dei Cavalieri, 7, 56124, Pisa, Italy.
2
Wellcome Trust/CRUK Gurdon Institute, Tennis Court Road, Cambridge, CB2 1QN, UK.
3
Department of Surgery and Translational Medicine, University of Florence, Florence, Italy.
4
Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge, CB2 0RE, UK.
5
Institute of Clinical Physiology CNR, Via Moruzzi 1, 56124, Pisa, Italy.
6
University of Nice Sophia-Antipolis, Parc Valrose, 28 Avenue Valrose, F-06108, Nice, France.
7
Genomics Facility, European Brain Research Institute (EBRI) "Rita Levi-Montalcini", Via del Fosso di Fiorano 64, 00143, Rome, Italy.
8
Institute of Translational Pharmacology, CNR, Via del Fosso del Cavaliere 100, 00133, Rome, Italy.
9
Scuola Normale Superiore of Pisa, Piazza dei Cavalieri, 7, 56124, Pisa, Italy. federico.cremisi@sns.it.
10
Institute of Biomedical Technologies (ITB), National Research Council (CNR) of Pisa, Via Moruzzi 1, 56124, Pisa, Italy. federico.cremisi@sns.it.

Abstract

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.

PMID:
27154007
PMCID:
PMC4858858
DOI:
10.1186/s13059-016-0952-x
[Indexed for MEDLINE]
Free PMC Article

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