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

Takashi Ishiuchi, Rocio Enriquez-Gasca, Eiji Mizutani, Ana Boškoviä, Celine Ziegler-Birling, Diego Rodriguez-Terrones, Teruhiko Wakayama, Juan M. Vaquerizas, Maria Elena Torres-Padilla

Research output: Contribution to journalArticle

94 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)662-671
Number of pages10
JournalNature Structural and Molecular Biology
Volume22
Issue number9
DOIs
Publication statusPublished - Sep 3 2015
Externally publishedYes

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Chromatin Assembly and Disassembly
Down-Regulation
Embryonic Structures
Embryonic Stem Cells
Endogenous Retroviruses
Histones
Genes

All Science Journal Classification (ASJC) codes

  • Structural Biology
  • Molecular Biology

Cite this

Ishiuchi, T., Enriquez-Gasca, R., Mizutani, E., Boškoviä, A., Ziegler-Birling, C., Rodriguez-Terrones, D., ... Torres-Padilla, M. E. (2015). Early embryonic-like cells are induced by downregulating replication-dependent chromatin assembly. Nature Structural and Molecular Biology, 22(9), 662-671. https://doi.org/10.1038/nsmb.3066

Early embryonic-like cells are induced by downregulating replication-dependent chromatin assembly. / Ishiuchi, Takashi; Enriquez-Gasca, Rocio; Mizutani, Eiji; Boškoviä, Ana; Ziegler-Birling, Celine; Rodriguez-Terrones, Diego; Wakayama, Teruhiko; Vaquerizas, Juan M.; Torres-Padilla, Maria Elena.

In: Nature Structural and Molecular Biology, Vol. 22, No. 9, 03.09.2015, p. 662-671.

Research output: Contribution to journalArticle

Ishiuchi, T, Enriquez-Gasca, R, Mizutani, E, Boškoviä, A, Ziegler-Birling, C, Rodriguez-Terrones, D, Wakayama, T, Vaquerizas, JM & Torres-Padilla, ME 2015, 'Early embryonic-like cells are induced by downregulating replication-dependent chromatin assembly', Nature Structural and Molecular Biology, vol. 22, no. 9, pp. 662-671. https://doi.org/10.1038/nsmb.3066
Ishiuchi T, Enriquez-Gasca R, Mizutani E, Boškoviä A, Ziegler-Birling C, Rodriguez-Terrones D et al. Early embryonic-like cells are induced by downregulating replication-dependent chromatin assembly. Nature Structural and Molecular Biology. 2015 Sep 3;22(9):662-671. https://doi.org/10.1038/nsmb.3066
Ishiuchi, Takashi ; Enriquez-Gasca, Rocio ; Mizutani, Eiji ; Boškoviä, Ana ; Ziegler-Birling, Celine ; Rodriguez-Terrones, Diego ; Wakayama, Teruhiko ; Vaquerizas, Juan M. ; Torres-Padilla, Maria Elena. / Early embryonic-like cells are induced by downregulating replication-dependent chromatin assembly. In: Nature Structural and Molecular Biology. 2015 ; Vol. 22, No. 9. pp. 662-671.
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