Human naive stem cell models reveal the role of FGF signalling in hypoblast specification in the human embryo
Dattani, A.; Simon, E. C.; Radley, A.; Heydari, T.; Taheriabkenar, Y.; Carlisle, F.; Lin, S.; Mill, J.; Zandstra, P. W.; Nichols, J.; Guo, G.
Show abstract
The hypoblast is an essential extra-embryonic tissue set aside within the inner cell mass early in mammalian embryo development, in the blastocyst. Research with human embryos is challenging. Thus, stem cell models that reproduce hypoblast differentiation provide valuable alternatives. We show here that human naive PSC to hypoblast differentiation proceeds via reversion to a transitional ICM-like state, from which hypoblast emerges in concordance with the trajectory in human blastocysts. We identified a window when fibroblast growth factor (FGF) signalling is critical for hypoblast specification. Revisiting FGF signalling in human embryos revealed that inhibition in the early blastocyst suppresses hypoblast formation. In vitro, the induction of hypoblast is synergistically enhanced by limiting trophectoderm and epiblast fates. This finding revises previous reports and establishes a conservation in lineage specification between mouse and human. Overall, this study demonstrates the utility of human naive PSC-based models in elucidating mechanistic features of early human embryogenesis.
Matching journals
The top 4 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- High resolution multi-scale profiling of embryonic germ cell-like cells derivation reveals pluripotent state transitions in humans 97%
- Differentiation Success of Reprogrammed Cells is Heterogenous In Vivo and Modulated by Somatic Cell Identity Memory 97%
- Developmental regulation of endothelial-to-hematopoietic transition from induced pluripotent stem cells 96%
Similar papers in this journal
- Eomes restricts Brachyury functions at the onset of mammalian gastrulation 95%
- NGN3 oscillatory expression controls the timing of human pancreatic endocrine differentiation 95%
- Comparative analysis of rhesus macaque and human placental organoids highlights evolutionary differences in placentation 95%
Similar papers in this journal
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.