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Stochasticity and the Molecular Mechanisms of Induced Pluripotency

Figure 3

Differentiation from pluripotent stem cell to terminal osteoblast occurs either directly or through a hierarchy of increasingly committed cell types.

In all panels blue indicates equilibrium OCT4/SOX2 expression; red indicates equilibrium NANOG expression; green indicates equilibrium SOX9 expression; dashed purple indicates equilibrium PPAR-γ expression; and black indicates equilibrium RUNX2 expression. The vertical grey dotted lines mark the points when a differentiation event occurs. These figures should be read left to right since they illustrate stimulus increasing with time. (a) Differentiation straight from a pluripotent state to a terminal ostoblastic state (model parameter values: k₀ = 10, k₁₁ = 1, k₁₂ = 0.5, k₂ = 1, k₃ = 0.9, k_PL = 2.5, , , k_LL = 1, m = 0.875, b = 0.1); (b) Differentiation straight from a pluripotent state to a terminal ostoblastic state via a primed state (model parameter values: k₀ = 5, k₁₁ = 1, k₁₂ = 0.5, k₂ = 5, k₃ = 0.9, k_PL = 0.5, , , k_LL = 1, m = 0.625, b = 0.1); (c) Differentiation from a pluripotent state to a terminal osteoblastic state through a hierarchy of increasingly committed tissue-specific progenitors (model parameter values: k₀ = 25, k₁₁ = 1, k₁₂ = 0.5, k₂ = 3, k₃ = 0.9, k_PL = 10, , , k_LL = 1, m = 0.75, b = 0.1); (d) Differentiation from a pluripotent state to a terminal osteoblastic through a hierarchy of increasingly committed tissue-specific progenitors via a primed state (model parameter values: k₀ = 20, k₁₁ = 1, k₁₂ = 0.5, k₂ = 7, k₃ = 0.9, k_PL = 0.1, , , k_LL = 0.75, m = 0.575, b = 0.1). Video versions of these bifurcation diagrams are given in the supplementary materials (Videos S1, S2, S3, S4). Details of the biological meaning of each of the model parameters are given in the supplementary materials (Text S1).

doi: https://doi.org/10.1371/journal.pone.0003086.g003