Ling Shuai

State Key Laboratory of Chemical Medicinal Biology, Nankai University, China

The discovery of unrestricted lineage potential in human naïve epiblast cells has opened new avenues for studying early human development. While  conventional  primed  human  embryonic  stem   cells  (hESCs) exhibit limited capacity to generate extraembryonic lineages, we show that    primed    haploid    hESCs    (hahESCs)    possess    expanded developmental    potential,     efficiently    differentiating     into    both trophoblast and hypoblast lineages. Remarkably, hahESCs are capable

of self-organizing into blastocyst-like structures (haBlastoids) that progress through peri- and early   post-implantation   stages.    From    haBlastoids,   we   derive    haploid   embryonic    and extraembryonic stem cell lines representing all three blastocyst lineages. Capitalizing on this property, as a proof of concept, we establish a robust platform for functional genetic screening using haploid trophoblast stem cells derived from haBlastoids and identify critical regulators of syncytiotrophoblast specification. Together, our findings reveal the intrinsic lineage plasticity of hahESCs and establish a versatile, genetically tractable haploid system for investigating early human embryogenesis and lineage-specific gene function.