A molecular roadmap for the emergence of early-embryonic-like cells in culture

Diego Rodriguez-Terrones, Xavier Gaume, Takashi Ishiuchi, Amélie Weiss, Arnaud Kopp, Kai Kruse, Audrey Penning, Juan M. Vaquerizas, Laurent Brino, Maria Elena Torres-Padilla

Research output: Contribution to journalArticlepeer-review

37 Citations (Scopus)

Abstract

Unlike pluripotent cells, which generate only embryonic tissues, totipotent cells can generate a full organism, including extra-embryonic 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.

Original languageEnglish
Pages (from-to)106-119
Number of pages14
JournalNature genetics
Volume50
Issue number1
DOIs
Publication statusPublished - Jan 1 2018

All Science Journal Classification (ASJC) codes

  • Genetics

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