GSE200958
Epiblast inducers capture mouse Trophectoderm Stem Cells in vitro and pattern blastoids for implantation in utero. [scRNAseq]
The embryo instructs the allocation of cell states to spatially regulate growth and functions. In the blastocyst, the formation and divergence of the trophoblast lineage ensures successful implantation and placental development. Here, we defined an optimal set of molecules secreted by the inner epiblast cells (inducers) that captures stable, highly self-renewing, pre-implantation-like mouse trophectoderm stem cells (TESCs). When exposed to suboptimal inducers, these stem cells form interconvertible subpopulations with reduced self-renewal, known as trophoblast stem cells (TSCs), and resembling peri-implantation progenitors. TECSs have an enhanced capacity to form blastoids that implant more efficiently in utero. We find that this enhanced capacity is due to epiblast inducers not only controlling trophoblast growth but also trophoblast secretion of WNT6/7B that stimulates uterine decidualization. Thus, the embryo leverages epiblast inductions to drive both the growth and decidualization potential of trophoblasts required for implantation and development. Overall design: To delineate the trophoblast stem cells (TSCs) heterogenity, single cell RNA seq analysis was performed. After the removal of FGF4 and TGFß1, TSCs were let to differentiate. Samples were collected at different time points (0, 4, 12, 24, 48 and 36 hours) and subsequentially sequenced. Library preparation was performed by following CEL-Seq2 protocol.