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Summary
Embryos develop in a concerted sequence of spatiotemporal arrangements of cells. In the preimplantation mouse embryo, the distribution of the cells in the inner cell mass evolves from a salt-and-pepper pattern to spatial segregation of two distinct cell types. The exact properties of the salt-and-pepper pattern have not been analyzed so far. We investigate the spatiotemporal distribution of NANOG- and GATA6-expressing cells in the ICM of the mouse blastocysts with quantitative three-dimensional single-cell-based neighborhood analyses. A combination of spatial statistics and agent-based modeling reveals that the cell fate distribution follows a local clustering pattern. Using ordinary differential equations modeling, we show that this pattern can be established by a distance-based signaling mechanism enabling cells to integrate information from the whole inner cell mass into their cell fate decision. Our work highlights the importance of longer-range signaling to ensure coordinated decisions in groups of cells to successfully build embryos.
Highlights
• The local cell neighborhood and global ICM population composition correlate
• ICM cells show characteristics of local clustering in early and mid mouse blastocysts
• ICM patterning requires integration of signals from cells beyond the first neighbors