Department of Developmental Genetics, Max Planck Institute for Molecular Genetics, 14195 Berlin, Germany.
Department of Genome Regulation, Max Planck Institute for Molecular Genetics, 14195 Berlin, Germany.
Science. 2020 Dec 11;370(6522). 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.
胚胎植入后发育是一个高度动态的过程，包括多个谱系决定和形态发生变化，这些变化在体内无法进行深入分析。我们发现多能性小鼠胚胎干细胞（mESCs）形成聚集物，这些聚集物在嵌入细胞外基质化合物后会诱导形成高度组织化的“主干样结构”（TLSs），其中包括神经管和体节。比较单细胞 RNA 测序分析证实，这个过程与小鼠发育非常相似，并遵循相同的逐步基因调控程序。TLSs 形成额外的神经管，反映了胚胎突变表型，化学调节可以诱导过多的体节形成。因此，TLSs 揭示了一个高级别的自我组织水平，并为在培养皿中研究胚胎植入后发育提供了一个强大的平台。
