[Using 2C-like cells to understand embryonic totipotency].

Totipotency is the ability of a cell to generate a whole organism, a property that characterizes the first embryonic cells, such as the zygote and the blastomeres. This review provides a retrospective on the progress made in the last decade in the study of totipotency, especially with the discovery of mouse ES cells expressing markers of the 2-cell stage (2C-like cells). This model has greatly contributed to a better understanding of the molecular mechanisms involved in totipotency (pioneer factors, epigenetic regulation, splicing, nuclear maturation).

A genetic screen identifies BEND3 as a regulator of bivalent gene expression and global DNA methylation.

Epigenetic mechanisms are essential to establish and safeguard cellular identities in mammals. They dynamically regulate the expression of genes, transposable elements and higher-order chromatin structures. Consequently, these chromatin marks are indispensable for mammalian development and alterations often lead to disease, such as cancer.

A genome-wide screen reveals new regulators of the 2-cell-like cell state.

In mammals, only the zygote and blastomeres of the early embryo are totipotent. This totipotency is mirrored in vitro by mouse '2-cell-like cells' (2CLCs), which appear at low frequency in cultures of embryonic stem cells (ESCs). Because totipotency is not completely understood, we carried out a genome-wide CRISPR knockout screen in mouse ESCs, searching for mutants that reactivate the expression of Dazl, a gene expressed in 2CLCs.