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Engineering signaling centers to trigger human trunk morphogenesis in vitro

ABSTRACT: Vertebrate trunk development is orchestrated by endogenous signaling centers that generate gradients of signals such as WNT and BMP to pattern cell fates and drive morphogenesis. Whether these cues alone can reconstitute human trunk-like morphogenesis in vitro remains unknown. Here, we present a synthetic embryology platform for high-throughput, spatio-temporal delivery of morphogen signals to epithelial cysts derived from human pluripotent stem cells. Transient WNT and BMP gradients are sufficient to drive the generation of axially elongating trunk-like structures containing a central neural tube flanked by axial, paraxial, intermediate, and lateral mesoderm. The geometry of the transient BMP signal exerts a lasting control over mediolateral patterning and bilateral symmetry. Patterning and morphogenesis are sustained by neuromesodermal and lateral plate mesoderm progenitors induced by the initial cues, which act as endogenous signaling centers. Together, these findings define a minimal spatial code sufficient to reconstitute trunk-like morphogenesis in a human stem cell–based model and establish a scalable platform for studying early human development and congenital disorders.

ORGANISM(S): Homo sapiens

PROVIDER: GSE306808 | GEO | 2026/09/15

REPOSITORIES: GEO

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