The extraembryonic endoderm of mammals is essential for nutritive support
of the foetus and patterning of the early embryo. Visceral and parietal endoderm are
major subtypes of this lineage with the former exhibiting most, if not all, of the
embryonic patterning properties. Extraembryonic endoderm (XEN) cell lines derived
from the primitive endoderm of mouse blastocysts represent a cell culture model of
this lineage, but are biased towards parietal endoderm in culture and in chimaeras.
Here, I further characterise XEN cells and show that these cell lines exhibit high
levels of heterogeneity. In an effort for XEN cells to adopt visceral endoderm
character different aspects of the in vivo environment were mimicked. I found that
BMP4 and laminin promote a mesenchymal-to-epithelial transition of XEN cells
with upregulation of epithelial markers and downregulation of mesenchymal
markers. Gene expression analysis showed the differentiated XEN cells most
resembled extraembryonic visceral endoderm. Correspondingly, inhibition of Erk
and BMP signalling drives XEN cells toward parietal endoderm fate. Finally, I show
that BMP4 treatment of freshly isolated parietal endoderm from Reichert’s
membrane promotes its visceral endoderm differentiation. This suggests that parietal
endoderm is still developmentally plastic and can be transdifferentiated to a visceral
endoderm in response to BMP. Generation of visceral endoderm from XEN cells
uncovers the true potential of these blastocyst-derived cells and is a significant step
towards modelling early developmental events ex vivo