Fig. 6. Jag1 bifurcates cell fates by mediating strong cis-interaction.

a Summary schematic diagram for the necessity of cis-interaction in pancreatic cell fate segregation. Successful cell fate bifurcation requires a certain level of cis-interaction. The heatmap shows the distribution of amplitude of Hes1 in simulated pancreas with different cis-interaction rate. Each column corresponds to one specific value of the cis-interaction rate. Cells maintain intermediate Hes1 oscillation amplitudes with low cis-interaction, while either high or low Hes1 oscillation amplitudes are seen with increased cis-interaction. b Summary schematic diagram for cell fate segregation failure without Jag1 regardless of the cis-interaction rate. With high cis-interaction rate (0.4), cell fate segregation is only partially achieved and some cells still fail to exit the MPC state and maintain an intermediate amplitude of Hes1. c Model predicts that increased expression of Jag1 rescues cell fate segregation at low cis-interaction rate. With γ₁ = 0.2, a few cells in wild type (blue dot, a_J = 1.0) pancreas can differentiate into BP fate or PAC fate, with Jag1 deficiency (red square, a_J = 0), the cells maintain MPC fate and with increased Jag1 (orange square, a_J = 4.0), the cells adopt a BP or PAC fate except for very few cells that maintain an MPC fate. d Model predicts that expression of Jag1 facilitates cell fate segregation at high cis-interaction rate. With γ₁ = 0.38, Jag1 deficiency causes a few cells to fail to differentiate and maintain MPC fate. With increased Jag1 (a_J = 1.2 is shown), the cells adopt a BP or PAC fate like the wild type. e MPC state is maintained by low Jag1 expression at the beginning of pancreatic development. The trans-interaction between cells and Hes1 oscillation are key factors for MPC fate maintenance. f Tip-trunk differentiation happens when Jag1 rises and mediates strong cis-interaction. Cell fate symmetry is broken by cis-interaction and strengthened trans-interaction.