TY - JOUR
T1 - Early embryonic-like cells are induced by downregulating replication-dependent chromatin assembly
AU - Ishiuchi, Takashi
AU - Enriquez-Gasca, Rocio
AU - Mizutani, Eiji
AU - Boškoviä, Ana
AU - Ziegler-Birling, Celine
AU - Rodriguez-Terrones, Diego
AU - Wakayama, Teruhiko
AU - Vaquerizas, Juan M.
AU - Torres-Padilla, Maria Elena
N1 - Funding Information:
We thank G. Almouzni and J.P. Quivy (Institut Curie) for providing antibodies to p150 and p60 and for helpful discussions, M. Takeichi (RIKEN Center for Developmental Biology) for pCAG-IRES-Hygro vector, S. Matoba for sharing the list of RRRs, M. Oginuma for help with embryo analysis, B. Jost, M. Philips and S. Vicaire from the Sequencing facility of the Institut Génétique Biologie Moléculaire Cellulaire, C. Ebel for support with FACS, M. Koch for advice on imaging, C. Noll for help in western blotting analysis, R. Diaz-Uriarte for statistical advice, C. Hug for help with code testing, P. André and M. Wattenhofer-Donze from the Institut Clinique de la Souris (ICS) for help with ES-cell work and A.J. Bannister for critical reading of the manuscript. M.-E.T.-P. acknowledges funding from EpiGeneSys NoE, ERC-Stg ‘NuclearPotency’, the FP7 Marie-Curie Actions ITN Nucleosome4D, the European Molecular Biology Organization Young Investigator Programme and the Fondation Schlumberger pour l’Education et la Recherche. J.M.V. acknowledges funding from EpiGeneSys NoE, Deutsche Forschungsgemeinschaft Cells-in-Motion Cluster of Excellence (EXC 1003–CiM), University of Münster and the Max Planck Society. Work in T.W.’s laboratory is funded through KAKENHI 23248048 and the Takeda Science Foundation. T.I. is supported as a recipient of postdoctoral fellowships from Uehara Memorial Foundation and Human Frontier Science Programme, and A.B. was supported as a recipient of a fellowship from the Association pour la Recherche Contre le Cancer. D.R.-T. is supported by a Dirección General de Cooperación e Internacionalización fellowship from the National University of Mexico. R.E.-G. is a member of the graduate school International Max Planck Research School–Molecular Biomedicine, Münster, Germany. This work received partial support from ANR-10-LABX-0030-INRT.
Publisher Copyright:
© 2015 Nature America, Inc. All rights reserved.
PY - 2015/9/3
Y1 - 2015/9/3
N2 - Cellular plasticity is essential for early embryonic cells. Unlike pluripotent cells, which form embryonic tissues, totipotent cells can generate a complete organism including embryonic and extraembryonic tissues. Cells resembling 2-cell-stage embryos (2C-like cells) arise at very low frequency in embryonic stem (ES) cell cultures. Although induced reprogramming to pluripotency is well established, totipotent cells remain poorly characterized, and whether reprogramming to totipotency is possible is unknown. We show that mouse 2C-like cells can be induced in vitro through downregulation of the chromatin-assembly activity of CAF-1. Endogenous retroviruses and genes specific to 2-cell embryos are the highest-upregulated genes upon CAF-1 knockdown. Emerging 2C-like cells exhibit molecular characteristics of 2-cell embryos and higher reprogrammability than ES cells upon nuclear transfer. Our results suggest that early embryonic-like cells can be induced by modulating chromatin assembly and that atypical histone deposition may trigger the emergence of totipotent cells.
AB - Cellular plasticity is essential for early embryonic cells. Unlike pluripotent cells, which form embryonic tissues, totipotent cells can generate a complete organism including embryonic and extraembryonic tissues. Cells resembling 2-cell-stage embryos (2C-like cells) arise at very low frequency in embryonic stem (ES) cell cultures. Although induced reprogramming to pluripotency is well established, totipotent cells remain poorly characterized, and whether reprogramming to totipotency is possible is unknown. We show that mouse 2C-like cells can be induced in vitro through downregulation of the chromatin-assembly activity of CAF-1. Endogenous retroviruses and genes specific to 2-cell embryos are the highest-upregulated genes upon CAF-1 knockdown. Emerging 2C-like cells exhibit molecular characteristics of 2-cell embryos and higher reprogrammability than ES cells upon nuclear transfer. Our results suggest that early embryonic-like cells can be induced by modulating chromatin assembly and that atypical histone deposition may trigger the emergence of totipotent cells.
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U2 - 10.1038/nsmb.3066
DO - 10.1038/nsmb.3066
M3 - Article
C2 - 26237512
AN - SCOPUS:84940990521
SN - 1545-9993
VL - 22
SP - 662
EP - 671
JO - Nature Structural and Molecular Biology
JF - Nature Structural and Molecular Biology
IS - 9
ER -