Cell_Fate_Proportions_BSDB.pdf

We present an embryonic stem cell model for cell differentiation in the mammalian preimplantation embryo, in which robust proportions of two differentiated cell types are specified from a wide range of experimentally controlled initial conditions in the precursor state. Using mutant analysis, we demonstrate that recursive cell-cell communication via fibroblast growth factor 4 (FGF4) underlies this robust proportioning. We furthermore show that communicating cell populations re-establish mixtures of the two cell types following flow-sorting of one cell type, indicating that cell-cell communication not only generates, but also maintains specific proportions of differentiated cell types. These experimental results can be explained theoretically by the self-organizing dynamics of the intercellular network established by FGF4, in which a heterogeneous attractor emerges in the communicating population. Cell-cell communication may underlie the robust behavior of cell populations despite uncertainty in initial conditions in precursor cells in a wide range of differentiation events in development and homeostasis.