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Nat Struct Mol Biol. 2015 Sep;22(9):662-71. doi: 10.1038/nsmb.3066. Epub 2015 Aug 3.

Early embryonic-like cells are induced by downregulating replication-dependent chromatin assembly.

Author information

1
Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS UMR7104 and INSERM U964, Illkirch, France.
2
Max Planck Institute for Molecular Biomedicine, Münster, Germany.
3
Faculty of Life and Environmental Sciences, University of Yamanashi, Yamanashi, Japan.

Abstract

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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PMID:
26237512
DOI:
10.1038/nsmb.3066
[Indexed for MEDLINE]
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