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Modelling interactions between somites and neural tube with human Trunk-like Structures (hTLS)

ABSTRACT: Human stem cell-based embryo-like models have opened new avenues of research into the principles of embryonic development using experimentally amenable in vitro systems. One of the benefits of embryo-like models over organoids is their multilineage differentiation, which allows the co-development of different populations and interaction between tissues. Here, we develop a method of generating somite- and neural tube-containing models, called human Trunk-like Structures (hTLS). These hTLS contain SOX2+ TBXT+ neuromesodermal progenitors, presomitic mesoderm, and somitic epithelial tissues, alongside a neural tube structure. As well as the expression of Wnt/FGF ligands posteriorly and Retinoic Acid (RA) pathway components anteriorly, we observe oscillatory HES7 expression, and show that increasing exposure to a Sonic Hedgehog signalling agonist (SAG) increasingly ventralises tissue identity. Additionally, we show that RA and noncanonical Wnt interactions likely occur between the somites and neural tube. In particular, we observe medially-localised ALDH1A2 expression in the somites - at the interface with the neural tube – which we validated in mouse embryos, whereas in somite-only structures, ALDH1A2 is anteroposteriorly polarised. This suggests that interactions between the neural tube and the somites might be responsible for mediolateral somitic organisation, both in vitro and in vivo, and highlights the value of embryo models to reveal insights into mammalian tissue co-development.

ORGANISM(S): Homo sapiens

PROVIDER: GSE268451 | GEO | 2025/10/01

REPOSITORIES: GEO

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