Cell Position-Associated Division Orders and Cell Cycle Durations Shape Asymmetric Trajectories of Cell Fates and Morphological Events in Pre- and Peri-implantation Mouse Embryos
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A central question in developmental biology is how spatiotemporal embryo morphological events and cell differentiation are precisely coordinated to eventually develop into a mature organism. Previous research has shown cell positions and asymmetric division stages are related to cell lineage specification since morula stage. However, the detailed spatiotemporal dynamics and histories of embryonic cells and their relations with cell lineage specification remain incompletely understood from the onset of embryo development onward. My study on in-vitro embryos showed that continuous live cell tracking mapped community-like patterns in cell origin and differentiation. Cell positions, cell temporal factors (such as cell division order and cell cycle) and their histories intricately interacted over pre-and peri-implantation stages. These interactions of spatiotemporal cellular activities directed embryo morphological events and asymmetric cell lineage origin and differentiation throughout 2-cell to around 100-cell stage. In conclusion, this study provides comprehensive insights into the cellular spatiotemporal dynamics of cell inheritance and differentiation during pre-and peri-implantation morphological events and cell lineage specification. By longitudinally integrating spatial and temporal parameters relating to early embryogenesis, the findings not only bridge divergent explanations stemmed from different studies in the field but also offers a refined foundation for evaluating embryo potential and improving outcomes in assisted reproductive technologies, stem cell research, and regenerative medicine.
Summary
The earliest stage of embryo development, from the fertilised zygote to the implantation-ready blastocyst, is central not only to understanding embryogenesis, but also to cell totipotency, pluripotency, and the establishment of stem-cell-based models and organoids. After more than two centuries of study, the field has accumulated extensive knowledge of this process, and many researchers now consider its major features largely resolved. In parallel, diverse methodological approaches have yielded multiple theoretical models, some of which have become dominant and appear to foreclose alternative interpretations. This work offers novel insights into pre-and peri-implantation development, from the 2-cell stage through to beyond the 100-cell stage. Because it challenges prevailing models of cell lineage specification during the first three lineages, the conduction, submission of this work and its publication have met with significant delays, sustained obstruction since at least 2022. To prevent further erosion of its novelty and, more importantly, to contribute new knowledge to the field, the work is shared here as a preprint.
