Rodriguez-Terrones, D. ; Gaume, X. ; Ishiuchi, T. ; Weiss, A.R.* ; Kopp, A.* ; Kruse, K.* ; Penning, A. ; Vaquerizas, J.M.* ; Brino, L.* ; Torres-Padilla, M.E.
A molecular roadmap for the emergence of early-embryonic-like cells in culture.
Nat. Genet. 50, 106-119 (2017)
Unlike pluripotent cells, which generate only embryonic tissues, totipotent cells can generate a full organism, including extraembryonic tissues. A rare population of cells resembling 2-cell-stage embryos arises in pluripotent embryonic stem (ES) cell cultures. These 2-cell-like cells display molecular features of totipotency and broader developmental plasticity. However, their specific nature and the process through which they arise remain outstanding questions. Here we identified intermediate cellular states and molecular determinants during the emergence of 2-cell-like cells. By deploying a quantitative single-cell expression approach, we identified an intermediate population characterized by expression of the transcription factor ZSCAN4 as a precursor of 2-cell-like cells. By using a small interfering RNA (siRNA) screen, we identified epigenetic regulators of 2-cell-like cell emergence, including the non-canonical PRC1 complex PRC1.6 and the EP400-TIP60 complex. Our data shed light on the mechanisms that underlie exit from the ES cell state toward the formation of early-embryonic-like cells in culture and identify key epigenetic pathways that promote this transition.
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Publication type
Article: Journal article
Document type
Scientific Article
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Keywords
Polycomb Repressive Complex; Pluripotent Stem-cells; Ground-state Pluripotency; Mouse Embryos; Es Cells; Preimplantation Embryos; Sequencing Data; Chromatin; Genes; Expression
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Language
english
Publication Year
2017
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2017
ISSN (print) / ISBN
1061-4036
e-ISSN
1546-1718
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Volume: 50,
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Pages: 106-119
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Nature Publishing Group
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New York, NY
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Peer reviewed
POF-Topic(s)
30204 - Cell Programming and Repair
Research field(s)
Stem Cell and Neuroscience
PSP Element(s)
G-506200-001
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Erfassungsdatum
2017-12-27