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bioRxiv · 10.1101/2020.03.04.974949

Mouse embryonic stem cells self-organize into trunk-like structures with neural tube and somites

Veenvliet, J. V.·Bolondi, A.·Kretzmer, H.·Haut, L.·Scholze-Wittler, M.·Schifferl, D.·Koch, F.·Pustet, M.·Heimann, S.·Buschow, R.·Wittler, L.·Timmermann, B.·Meissner, A.·Herrmann, B. G.
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Abstract

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 summaryA platform for generating trunk-like-structures with precursors of spinal cord, bone and muscle from stem cells in a dish

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Veenvliet, J. V., Bolondi, A., Kretzmer, H., Haut, L., Scholze-Wittler, M., Schifferl, D., Koch, F., Pustet, M., Heimann, S., Buschow, R., Wittler, L., Timmermann, B., Meissner, A., Herrmann, B. G.. 2020-03-04. Mouse embryonic stem cells self-organize into trunk-like structures with neural tube and somites. https://doi.org/10.1101/2020.03.04.974949

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