Lateral plate mesoderm directs human amnion and ventral skin organoid formation

Here, we advance this approach by controlling the size and composition of cranial skin organoids (cSkOs) and incorporating lateral plate mesoderm (LPM) cells to create ventral skin organoids (vSkOs) and human amnion-like structures, termed Amnioids.

Amnioids, resembling their extra-embryonic counterparts, are avascular and rapidly expand into large, hairless cysts, while vSkOs develop primitive vasculature and numerous hair follicles. Single-cell RNA sequencing identified distinct gene expression patterns and developmental trajectories, revealing the critical roles of Wnt and YAP/Hippo signaling in directing divergent fates. Functional experiments underscored the importance of mechanical forces and mesenchymal-epithelial interactions in shaping tissue growth and organization.