Abstract  Concept & Model  Requirements  Genetic_circuit  Works  About_our_team

What is necessary for "Balanced differentiation"?

The most important and underlying point of our model is that the system is stable against environmental changes when two types of differentiated individuals coexist, called "Balanced differentiation." Our project has aimed at this "Balanced differentiation" but not dynamic equilibrium such as chemical ones.
To achieve this “Balanced differentiation", our model requires
1. differentiation(=bistability) generated by mutual-inhibition circuit.
2. cell-cell communication by quorum sensing

Fig.1: Differentiation(=bistability)
Cells with the same gene take either of two differentiated states, A (worker, red) or B (idler, green) stably.

1. Differentiation(=bistability)

~ at an individual level ~

For "balanced differentiation" in our model, two types of cells should coexist stably. Therefore, cells with THE SAME GENE SET need to take either of TWO DIFFERENTIATED STATES, A (Worker) or B (Idler) in our project as shown in Fig. 1. In order to distinguish from dynamic stability, "balanced differentiation" must be achieved by two distinct states inconvertible each other. This bistability can be achieved by mutual-inhibition circuit.

2. Cell-cell communication

When this balanced differentiation is disrupted, by removing all the A types for example, the rest individual B cells sense the change. Their differentiated states become unstable as if they become upset. Then all cells dedifferentiate, but after a while, redifferentiation is triggered by cell-cell communication. As a result, at a certain ratio of A and B again, the whole system comes back to a stable state.

Fig.2: Cell-cell communication
Intercellular interaction is established by communication molecule AHL. When enough AHL is produced by the workers, the idlers are stable; however, if it is not ~ communication being interrupted, ~ they dedifferentiate. Thus, cells can sense the surrounding cell types.