TY - JOUR T1 - Mouse embryonic stem cells self-organize into trunk-like structures with neural tube and somites JF - bioRxiv DO - 10.1101/2020.03.04.974949 SP - 2020.03.04.974949 AU - Veenvliet, Jesse V AU - Bolondi, Adriano AU - Kretzmer, Helene AU - Haut, Leah AU - Scholze-Wittler, Manuela AU - Schifferl, Dennis AU - Koch, Frederic AU - Pustet, Milena AU - Heimann, Simon AU - Buschow, Rene AU - Wittler, Lars AU - Timmermann, Bernd AU - Meissner, Alexander AU - Herrmann, Bernhard G Y1 - 2020/01/01 UR - http://biorxiv.org/content/early/2020/03/04/2020.03.04.974949.abstract N2 - Post-implantation embryogenesis is a highly dynamic process comprising multiple lineage decisions and morphogenetic changes inaccessible to deep analysis in vivo. Mouse embryonic stem cells (mESCs) can form aggregates reflecting the post-occipital embryo (gastruloids), but lacking proper morphogenesis. Here we show that embedding of aggregates derived from mESCs in an extracellular matrix compound results in Trunk-Like-Structures (TLS) with a high level of organization comprising a neural tube and somites. Comparative single-cell RNA-seq analysis demonstrates that TLS execute gene-regulatory programs in an embryo-like order, and generate primordial germ cell like cells (PGCLCs). TLS lacking Tbx6 form ectopic neural tubes, mirroring the embryonic mutant phenotype. ESC-derived trunk-like structures thus constitute a novel powerful in vitro platform for investigating lineage decisions and morphogenetic processes shaping the post-implantation embryo.One sentence summary A platform for generating trunk-like-structures with precursors of spinal cord, bone and muscle from stem cells in a dish ER -