Figure 3. Hybrid E/M and D/U (stem-like) phenotypes overlap over a large variation of EMT-STEM circuit coupling strength.

(A) For L_EXT = 10³ molecules and no EMT-STEM coupling λ_LIM−28 = λ_ZEM = 1 (first considered condition), the cell expresses a hybrid E/M state (see the intersection of the red dotted line with the diagram's continuous lines). (B) EMT state diagram over variation of fold-changes for let-7 inhibition on ZEB (λ_ZEM, x-axis) and micro-RNA-200 inhibition on LIN-28 (λ_ZEM−28, y-axis) and for L_EXT = 10³ (panel A). The cell phenotype is described by the state of the EMT module. (C) STEM phenotypic characterization diagram for the conditions of panel A. The cell phenotype is described by the state of the STEM module (Down: D, Stem: STEM, Up: U). (D) Superimposition of the stability regions of hybrid E/M state (panel B) and D/U state (panel C) for the conditions of panel A. Labels highlight the regions where the hybrid E/M and/or stem-like D/U are observed. This diagram does not label every combination of EMT and STEM phenotypes but only highlight regions where either hybrid E/M or stem-like D/U (or both) are expressed. (E) For L_EXT = 510³ molecules and no EMT-STEM coupling λ_ZEM−28 = λ_ZEM = 1 (second considered condition), the cell expresses a monostable mesenchymal phenotype. (F) EMT state diagram for L_EXT = 510³ (panel E). (G) STEM phenotypic characterization diagram for the conditions of panel E. (H) Superimposition of the stability regions of hybrid E/M state (panel F) and D/U state (panel G) for the conditions of panel E.