Mechanistic Model-Guided Study of Embryonic Morphogenesis

We utilize a finite element model of implantation mechanics to guide the in vitro micropatterning human embryonic stem cells to simulate in vivo stress gradients that form during development. Micropatterned stem cells showed early formation of GATA4+/SOX17+ primitive endoderm due to migration toward regions of high stress, while NANOG+/OCT4+ epiblast was retained in regions of low stress under spontaneous differentiation. Recently, Blakeley and colleagues used single cell RNA-Seq of human blastocysts to identify genes that are differentially expressed between primitive endoderm and epiblast cells. RNA-Seq analysis was used to show that our NANOG+/OCT4+ cells (stress-low region) cluster with epiblast markers. while GATA6+/SOX17+ cells (stress-high region) cluster with primitive endoderm markers. We also utalized these results to compare the GSEA to GSEA of late blastocyst data.