title: Early embryonic-like cells are induced by downregulating replication-dependent chromatin assembly.
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.
authors.affiliation: Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS UMR7104 and INSERM U964, Illkirch, France.
authors.forename: Takashi
authors.initials: T
authors.lastname: Ishiuchi
authors.affiliation: Max Planck Institute for Molecular Biomedicine, Münster, Germany.
authors.forename: Rocio
authors.initials: R
authors.lastname: Enriquez-Gasca
authors.affiliation: Faculty of Life and Environmental Sciences, University of Yamanashi, Yamanashi, Japan.
authors.forename: Eiji
authors.initials: E
authors.lastname: Mizutani
authors.affiliation: Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS UMR7104 and INSERM U964, Illkirch, France.
authors.forename: Ana
authors.initials: A
authors.lastname: Bošković
authors.affiliation: Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS UMR7104 and INSERM U964, Illkirch, France.
authors.forename: Celine
authors.initials: C
authors.lastname: Ziegler-Birling
authors.affiliation: Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS UMR7104 and INSERM U964, Illkirch, France.
authors.forename: Diego
authors.initials: D
authors.lastname: Rodriguez-Terrones
authors.affiliation: Faculty of Life and Environmental Sciences, University of Yamanashi, Yamanashi, Japan.
authors.forename: Teruhiko
authors.initials: T
authors.lastname: Wakayama
authors.affiliation: Max Planck Institute for Molecular Biomedicine, Münster, Germany.
authors.forename: Juan M
authors.initials: JM
authors.lastname: Vaquerizas
authors.affiliation: Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS UMR7104 and INSERM U964, Illkirch, France.
authors.forename: Maria-Elena
authors.initials: ME
authors.lastname: Torres-Padilla
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D042002:Chromatin Assembly and Disassembly; D005095:Exoribonucleases; D051379:Mice; D011506:Proteins / Q000037:antagonists & inhibitors*; D012097:Repressor Proteins; D012260:Ribonucleases; D039901:Totipotent Stem Cells / Q000502:physiology*
chemical_list: D011506:Proteins; D012097:Repressor Proteins; C489778:Cnot7 protein, mouse; D005095:Exoribonucleases; D012260:Ribonucleases