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The process controlling the diferentiation of stem, or progenitor, cells intoone specific functional direction is called lineage specification. An importantcharacteristic of this process is the multi-lineage priming, which requires thesimultaneous expression of lineage-specific genes. Prior to commitment to acertain lineage, it has been observed that these genes exhibit intermediatevalues of their expression levels. Multi-lineage differentiation has beenreported for various progenitor cells, and it has been explained through thebifurcation of a metastable state. During the differentiation process thedynamics of the core regulatory network follows a bifurcation, where themetastable state, corresponding to the progenitor cell, is destabilized and thesystem is forced to choose between the possible developmental alternatives.While this approach gives a reasonable interpretation of the cell fate decisionprocess, it fails to explain the multi-lineage priming characteristic. Here, wedescribe a new multi-dimensional switch-like model that captures both theprocess of cell fate decision and the phenomenon of multi-lineage priming. Weshow that in the symmetrical interaction case, the system exhibits a new typeof degenerate bifurcation, characterized by a critical hyperplane, containingan infinite number of critical steady states. This critical hyperplane may beinterpreted as the support for the multi-lineage priming states of theprogenitor. Also, the cell fate decision (the multi-stability and switchingbehavior) can be explained by a symmetry breaking in the parameter space ofthis critical hyperplane. These analytical results are confirmed by Monte-Carlosimulations of the corresponding chemical master equations.

Monte-Carlo Simulation of a Multi-Dimensional Switch-Like Model of Stem Cell Differentiation