  The process controlling the diferentiation of stem, or progenitor, cells into
one specific functional direction is called lineage specification. An important
characteristic of this process is the multi-lineage priming, which requires the
simultaneous expression of lineage-specific genes. Prior to commitment to a
certain lineage, it has been observed that these genes exhibit intermediate
values of their expression levels. Multi-lineage differentiation has been
reported for various progenitor cells, and it has been explained through the
bifurcation of a metastable state. During the differentiation process the
dynamics of the core regulatory network follows a bifurcation, where the
metastable state, corresponding to the progenitor cell, is destabilized and the
system is forced to choose between the possible developmental alternatives.
While this approach gives a reasonable interpretation of the cell fate decision
process, it fails to explain the multi-lineage priming characteristic. Here, we
describe a new multi-dimensional switch-like model that captures both the
process of cell fate decision and the phenomenon of multi-lineage priming. We
show that in the symmetrical interaction case, the system exhibits a new type
of degenerate bifurcation, characterized by a critical hyperplane, containing
an infinite number of critical steady states. This critical hyperplane may be
interpreted as the support for the multi-lineage priming states of the
progenitor. Also, the cell fate decision (the multi-stability and switching
behavior) can be explained by a symmetry breaking in the parameter space of
this critical hyperplane. These analytical results are confirmed by Monte-Carlo
simulations of the corresponding chemical master equations.
