By using an embedded 3D culture system, we successfully cultured cynomolgus monkey embryos ex utero for up to 25 days post-fertilization, and found that these cultured embryos largely recapitulated in vivo development. This allowed us to study various developmental processes such as neural induction, mesoderm differentiation, hematopoiesis, gut development, and germ-cell-like cell development in monkeys.
The third and fourth weeks of gestation in primates are marked by several developmental milestones, including gastrulation and the formation of organ primordia. However, our understanding of this period is limited due to restricted access to in vivo embryos. To address this gap, we developed an embedded 3D cul-ture system that allows for the extended ex utero culture of cynomolgus monkey embryos for up to 25 days post-fertilization. Morphological, histological, and single-cell RNA-sequencing analyses demonstrate that ex utero cultured monkey embryos largely recapitulated key events of in vivo development. With this platform, we were able to delineate lineage trajectories and genetic programs involved in neural induction, lateral plate mesoderm differentiation, yolk sac hematopoiesis, primitive gut, and primordial germ-cell-like cell develop-ment in monkeys. Our embedded 3D culture system provides a robust and reproducible platform for growing monkey embryos from blastocysts to early organogenesis and studying primate embryogenesis ex utero.
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