RT Journal Article SR Electronic T1 Embryonic signals perpetuate polar-like trophoblast stem cells and pattern the blastocyst axis JF bioRxiv FD Cold Spring Harbor Laboratory SP 510362 DO 10.1101/510362 A1 Frias-Aldeguer, Javier A1 Kip, Maarten A1 ViviƩ, Judith A1 Li, Linfeng A1 Alemany, Anna A1 Korving, Jeroen A1 Darmis, Frank A1 van Oudenaarden, Alexander A1 Van Blitterswijk, Clemens A. A1 Geijsen, Niels A1 Rivron, Nicolas C. YR 2019 UL http://biorxiv.org/content/early/2019/03/06/510362.abstract AB The early mammalian conceptus (blastocyst) comprises an outer trophoblast globe that forms an axis originating from the inner embryonic cells. From the mouse conceptus, Trophoblast stem cells (TSCs) are derived, which are in vitro analogues of early trophoblasts. Here, we show that TSCs contain plastic subpopulations reflecting developmental states ranging from pre-to post-implantation trophoblasts. However, upon exposure to a specific combination of embryonic inductive signals, TSCs globally acquire properties of pre-implantation polar trophoblasts (gene expression, self-renewal) juxtaposing the inner embryonic cells, and an enhanced, homogeneous epithelial phenotype. These lines of polar-like TSCs (pTSCs) represent a transcriptionally earlier state that more efficiently forms blastoids, whose inner embryonic cells then induce the patterning of gene expression along the embryonic-abembryonic axis. Altogether, delineating the requirements and properties of polar trophoblasts and blastocyst axis formation in vitro provides a foundation for the precise description and dissection of early development.