Dissecting crosstalk between embryonic and extra-embryonic tissues with stem cell co-culture [II]
Faithful embryogenesis requires the precise coordination between embryonic and extraembryonic tissues. Although embryonic and extraembryonic stem cells have been derived from several mammalian species including humans, they are cultured in different conditions, which makes it difficult to study their intercommunication. Here, by simultaneously activating FGF, TGF-ß and WNT pathways, we derived stable pluripotent stem cells (PSCs), trophoblast stem cells (TSCs) and extraembryonic endoderm stem cells (XENs) from mouse blastocysts under the same condition (FTW). Co-culture of PSCs and XENs in the same environment uncovered, among other interactions, a previously unrecognized control of proliferation of epiblast cells by extraembryonic endoderm cells. FTW condition also supported de novo derivation of XENs from cynomolgus monkey and human blastocysts, and enabled setting up co-culture of human iPSCs and XENs. Crosspieces comparison revealed conserved and divergent processes and genes regulating XENs and ligand-receptor interactions between pluripotent and extraembryonic endoderm cells. Our study establishes a unique stem cell co-culture strategy to examine embryonic and extraembryonic lineage crosstalk during early mammalian development, and opens the door for developing more faithful in vitro models and differentiation protocols. Overall design: Totally 7 samples were sequenced, including 1 mouse blastocyst sample, 1 mouse blastocyst derevation in FTW medium for 8 days sample, 1 FTW-mESCs sample, 1 FTW-mTSCs sample, 1 FTW-mXENs sample, and 2 replicates of FTW-mESCs/FTW-mTSCs/FTW-mXENs co-culture for 5 days samples.