Modeling aspects of human early post-implantation development with stem cells

Early post-implantation development in humans, often a 'black box' due to limited access to natural embryos, has recently been studied using integrated stem cell-based embryo models (SCBEMs) that include most, if not all, embryonic and extraembryonic cell types. However, these models face challenges in reproducibility, efficiency, genomic and epigenomic stability, and/or fidelity, necessitating further development and refinement. Here, we have optimized a method for generating SCBEMs by combining primed human pluripotent stem cells (hPSCs) with transgene-induced extraembryonic cells from naïve hPSCs. The resulting inducible SCBEMs (iSCBEMs) effectively mimic key features of early post-implantation human concepti, including the development of amniontic, yolk sac and chorionic cavities, differentiation of syncytiotrophoblast-like cells forming lacunae, bilaminar disk formation, the establishment of the A-P axis and early stages of gastrulation. Human iSCBEMs offer a valuable alternative for studying early human post-implantation development. Overall design: To investigate whether the generated iSCBEMs successfully mimic human post-implantation embryo development at the single-cell transcriptomic level, we subjected samples from Day 0 (starting cells), Day 3, Day 5, and Day 7 of the iSCBEM protocol to the 10x Genomics Chromium platform.