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

• Published in: Science (American Association for the Advancement of Science) Vol. 370; no. 6522
• Main Authors: Veenvliet, Jesse V, Bolondi, Adriano, Kretzmer, Helene, Haut, Leah, Scholze-Wittler, Manuela, Schifferl, Dennis, Koch, Frederic, Guignard, Léo, Kumar, Abhishek Sampath, Pustet, Milena, Heimann, Simon, Buschow, René, Wittler, Lars, Timmermann, Bernd, Meissner, Alexander, Herrmann, Bernhard G
• Format: Journal Article
• Language: English
• Published: United States The American Association for the Advancement of Science 11-12-2020
• Subjects: Accessibility; Aggregates; Animals; Bone morphogenetic proteins; Cell adhesion; Cell adhesion & migration; Cell adhesion molecules; Cell culture; Decision analysis; Differentiation; Embedding; Embryo cells; Embryogenesis; Embryonic Development - genetics; Embryonic Development - physiology; Embryonic growth stage; Embryos; Extracellular matrix; Fibronectin; Gene expression; Gene Expression Regulation, Developmental; Gene regulation; Gene sequencing; Image segmentation; Implantation; Individualized Instruction; Integrins; Mammals; Matrix protein; Mice; Mice, Knockout; Modulation; Molecular modelling; Morphogenesis; Mouse Embryonic Stem Cells - physiology; Mutants; Neural stem cells; Neural tube; Neural Tube - embryology; Ontogeny; Phenotypes; Polarity; Proteins; Pyridines - pharmacology; Pyrimidines - pharmacology; Rhythms; Ribonucleic acid; RNA; Sequence analysis; Signaling; Somites - embryology; Stem cells; Surgical implants; T-Box Domain Proteins - genetics; Ticks; Transcription; Transcriptomics; Tubes; Vertebrates; Wnt Proteins - antagonists & inhibitors
• ISSN: 0036-8075; 1095-9203
• DOI: 10.1126/science.aba4937

Post-implantation embryogenesis is a highly dynamic process comprising multiple lineage decisions and morphogenetic changes that are inaccessible to deep analysis in vivo. We found that pluripotent mouse embryonic stem cells (mESCs) form aggregates that upon embedding in an extracellular matrix compound induce the formation of highly organized "trunk-like structures" (TLSs) comprising the neural tube and somites. Comparative single-cell RNA sequencing analysis confirmed that this process is highly analogous to mouse development and follows the same stepwise gene-regulatory program.
knockout TLSs developed additional neural tubes mirroring the embryonic mutant phenotype, and chemical modulation could induce excess somite formation. TLSs thus reveal an advanced level of self-organization and provide a powerful platform for investigating post-implantation embryogenesis in a dish.