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Self-organized trunk-like-structures with somites and a neural tube

ABSTRACT: The post-implantation embryo is subject to extensive growth, morphogenetic changes and lineage decisions that take place in utero and are therefore difficult to deconstruct in vivo. A robust in vitro culture system that mimics post-implantation mouse development would pave the path towards understanding the dynamics of these processes and how they are coupled. Small aggregates of mouse embryonic stem cells (mESCs) can undergo gastrulation-like events and elongation in vitro, resulting in aggregates with gene expression domains that reflect the post-occipital embryo (gastruloids1–3). However, these ordered patterns of gene expression do not correlate with embryo-like morphogenesis. Here we show that mechano-chemical manipulation of the aggregates results in Trunk-Like-Structures (TLS) with a high level of organization of the embryonic tissue layers, including the formation of a neural tube and somites. Comparative single-cell RNA-Seq (scRNA-Seq) of TLS and embryos demonstrated the molecular complexity of TLS, confirmed embryo-like gene-regulatory programs, and unveiled the presence of primordial germ cell like cells (PGCLCs). Finally, Tbx6-/- TLS formed ectopic neural tubes, recapitulating the in vivo phenotype. These results suggest that TLS are a powerful platform to study the morphogenetic changes and lineage decisions during post-implantation development in space and time.

ORGANISM(S): Mus musculus

PROVIDER: GSE141175 | GEO | 2020/12/14

REPOSITORIES: GEO

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