image: Intercellular crosstalk within human preimplantation lineages
Credit: ©Science China Press
A research team led by Professors Yixuan Wang and Shaorong Gao from the School of Life Sciences and Technology at Tongji University has made significant progress in understanding early human embryonic development. Their findings, recently published in Science Bulletin, reconstruct a comprehensive communication network among human preimplantation lineages and integrate it with intracellular gene regulatory networks, thus offering vital insights into lineage specification and cell fate regulation during human embryonic development.
To overcome the limitations of natural human embryo samples, the team analyzed single-cell transcriptome data during the transition of human embryonic stem cells from the primed to the naive state. They found that intermediate subpopulations exhibit transcriptomic features corresponding to the epiblast (EPI), primitive endoderm (PrE), and trophectoderm (TE) lineages. These populations, termed iEPI, iPrE, and iTE, were used to construct a robust in vitro model faithfully recapitulating the early human blastocyst.
By applying CellChat, a computational tool for revealing cell-cell communications at a single cell level, the researchers mapped out a high-resolution signaling crosstalk network among the tri-lineages, including secreted signals, cell-cell contacts, and ECM–receptor interactions, and further deciphered the specific extracellular signal-stimulations encountered by each lineage.
Importantly, this study demonstrated that the receptor ERBB3-mediated NRG signaling within the extracellular signaling context encountered by TE cells plays an important role in TE lineage specification. These results were substantiated by the impaired trophectoderm differentiation, human blastoid formation, and natural embryo development from 8 cells to blastocyst under ERBB3-knockout/blockade condition. Moreover, through the gene co-expression analysis, this study bridged receptor-mediated extracellular stimuli with intracellular gene expression regulatory network and highlighted TFAP2C as a key downstream intracellular effector of the NRG1-ERBB3 axis. Overexpression of TFAP2C could significantly restore the impaired trophectoderm induction efficiency.
Collectively, this study reconstructs a comprehensive communication network among human preimplantation lineages and integrates it with intracellular gene regulatory networks, thus offering vital insights into lineage specification and cell fate regulation during human embryonic development.
See the article:
Intercellular crosstalk within human preimplantation lineages regulates trophectoderm specification
https://doi.org/10.1016/j.scib.2025.06.003
Journal
Science Bulletin