Characterization of computational pattern trajectories and comparison to
experimental patterns. (a) Description of rules governing modeling.
Red arrows, negative feedback; green arrows, positive feedback; small triangles
indicate a soluble morphogen gradient. (b) Hierarchal clustering
using a Ward linkage algorithm of the pattern trajectories for each parameter
set, annotated by rule (gray scale bar). (c) Ratio of the 1000-cell
to 250-cell differentiation rate. Blue represents slower differentiation in
1000-cellular aggregates, while red represents faster differentiation.
(d) Representative images of the differentiation trajectories
predicted by the competing paracrine rule (cells in blue are Oct4−,
cells in teal are Oct4+). (e) Percent differentiation for representative
250 (top) and 1000-cell (bottom) simulations. Red represents differentiation
induced via absence of inhibitor, while blue represents differentiation induced
via the agonist. (f) PCA projections indicating the best fits of the 250 (top)
and 1000-cell (bottom) experimental data (red) to the simulations (blue).