PT  - JOURNAL ARTICLE
AU  - Sophie M. Morgani
AU  - Jakob J. Metzger
AU  - Jennifer Nichols
AU  - Eric D. Siggia
AU  - Anna-Katerina Hadjantonakis
TI  - Micropattern differentiation of mouse pluripotent stem cells recapitulates embryo regionalized cell fate patterning
AID  - 10.1101/236562
DP  - 2018 Jan 01
TA  - bioRxiv
PG  - 236562
4099  - http://biorxiv.org/content/early/2018/01/19/236562.short
4100  - http://biorxiv.org/content/early/2018/01/19/236562.full
AB  - During gastrulation epiblast cells exit pluripotency as they specify and spatially arrange the three germ layers of the embryo. Similarly, human pluripotent stem cells (PSCs) undergo spatially organized fate specification on micropatterned surfaces. Since in vivo validation is not possible for the human, we developed a mouse PSC micropattern system and, with direct comparisons to mouse embryos, reveal the robust specification of distinct regional identities. BMP, WNT, ACTIVIN and FGF directed mouse epiblast-like cells to undergo an epithelial-to-mesenchymal transition and radially pattern posterior mesoderm fates. Conversely, WNT, ACTIVIN and FGF patterned anterior identities, including definitive endoderm. By contrast, epiblast stem cells, a developmentally advanced state, only specified anterior identities, but without patterning. The mouse micropattern system offers a robust scalable method to generate regionalized cell types present in vivo, resolve how signals promote distinct identities and generate patterns, and compare mechanisms operating in vivo and in vitro and across species.