biostudies-literatureWei YNICHD NIH HHSNIDDK NIH HHSNHLBI NIH HHSNHGRI NIH HHSNCI NIH HHSNIGMS NIH HHS5859-5875.e24https://www.ebi.ac.uk/biostudies/studies/S-EPMC10916932biostudies-literatureUnknown186(26)Embryogenesis necessitates harmonious coordination between embryonic and extraembryonic tissues. Although stem cells of both embryonic and extraembryonic origins have been generated, they are grown in different culture conditions. In this study, utilizing a unified culture condition that activates the FGF, TGF-β, and WNT pathways, we have successfully derived embryonic stem cells (FTW-ESCs), extraembryonic endoderm stem cells (FTW-XENs), and trophoblast stem cells (FTW-TSCs) from the three foundational tissues of mouse and cynomolgus monkey (Macaca fascicularis) blastocysts. This approach facilitates the co-culture of embryonic and extraembryonic stem cells, revealing a growth inhibition effect exerted by extraembryonic endoderm cells on pluripotent cells, partially through extracellular matrix signaling. Additionally, our cross-species analysis identified both shared and unique transcription factors and pathways regulating FTW-XENs. The embryonic and extraembryonic stem cell co-culture strategy offers promising avenues for developing more faithful embryo models and devising more developmentally pertinent differentiation protocols.CellDissecting embryonic and extraembryonic lineage crosstalk with stem cell co-culture.PMC10916932R21 CA259771R01 DK127037R01 CA263079R01 HL144969R01 HD103627UM1 HG011996R01 GM138565Xu LSun HXWu JZhang EYu LLiu JLin SLiu LShen QZhang JCi BSchmitz DAWei YSu TGuo LDing YJi WZhang XTakii SSakurai MZheng CTan TZhan LOkamura DfalseDissecting embryonic and extraembryonic lineage crosstalk with stem cell co-culture.Embryogenesis necessitates harmonious coordination between embryonic and extraembryonic tissues. Although stem cells of both embryonic and extraembryonic origins have been generated, they are grown in different culture conditions. In this study, utilizing a unified culture condition that activates the FGF, TGF-β, and WNT pathways, we have successfully derived embryonic stem cells (FTW-ESCs), extraembryonic endoderm stem cells (FTW-XENs), and trophoblast stem cells (FTW-TSCs) from the three foundational tissues of mouse and cynomolgus monkey (Macaca fascicularis) blastocysts. This approach facilitates the co-culture of embryonic and extraembryonic stem cells, revealing a growth inhibition effect exerted by extraembryonic endoderm cells on pluripotent cells, partially through extracellular matrix signaling. Additionally, our cross-species analysis identified both shared and unique transcription factors and pathways regulating FTW-XENs. The embryonic and extraembryonic stem cell co-culture strategy offers promising avenues for developing more faithful embryo models and devising more developmentally pertinent differentiation protocols.2023-01-01T00:00:00Z2023 Dec2025-04-04T20:27:57.457Z2025-04-04T20:27:57.457ZS-EPMC109169323805221310.1016/j.cell.2023.11.008