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Reconstituting epiblast-extraembryonic endoderm interactions restores anterior-ventral patterning in stem cell-based embryo models.

Created on 12 Nov 2025

Authors

Smirnova, N. P., Ponomartsev, S. V., Ali, T. M. L., Lycke, M., Chung, B. K., Ogaard, J., Melum, E., Veenvliet, J., Krauss, S.

Abstract

During mouse embryogenesis, the interactions between the epiblast and extraembryonic endoderm are critical for germ layer specification and body plan development. Gastruloids recapitulate aspects of gastrulation in the absence of morphogenic signals from the extraembryonic environment. This favors a predominantly posteriorized and dorsalized phenotype with a limited representation of embryonic lineages. Here, we develop and employ a co-aggregation (aggregoid) approach combining embryonic and extraembryonic endoderm-like cells to mimic spatial interactions in developing mouse embryos. The obtained embryo models show the appearance of a regionalized primitive streak-like structure that results in the formation of node and notochord, enriched endoderm populations, increased mesoderm diversity including cardiopharyngeal lineages and vascular endothelium in an overall anteriorized and ventralized phenotype. The work delineates a versatile strategy for refining stem cell-based embryo models to achieve specific morphotypes.

Preprint server: bioRxiv
The authors list and abstract were imported from bioRxiv on 12 Nov 2025.

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