Figure 6.

Impact of altering edge strengths on cell reprogramming landscape

(A) Schematic showing the reference and the altered gene regulatory network in which the link strength of SOX9 inhibiting TGFBR2 has been increased.

(B) Changes in bifurcation diagram on altering the circuit as shown in A. Blue solid lines show stable steady states whereas the red dashed line shows the unstable states for the reference bifurcation diagram. Green solid lines and orange dashed lines are the stable and unstable states for the altered GRN in A. Bidirectional arrow is indicative of direct transition of hepatocytes to cholangiocytes at higher levels of TGFβ ligand.

(C) Schematic showing the reference and the two cases of the gene regulatory network in which the link strength of SOX9 inhibiting c/EBPα has been decreased (Case 1) or increased (Case 2).

(D) Reference bifurcation diagram is shown in blue solid lines and red dashed lines. Bifurcation diagram for case 1 is shown in green solid line (hepatocyte state only) while the orange solid curve refers to case 2 (progenitor/cholangiocyte state only). Note that there are no unstable states in the green and the orange profiles indicating that only one fate is enabled by the parameter set.

(E) Schematic showing the changes in the landscape brought about by changing the strength of SOX9 suppression of c/EBPα in which for case 1 and case 2 only one stable state is allowed while for the reference case 2 stable states are possible.