Noisy signal propagation and amplification in phenotypic transition cascade of colonic cells

Like genes and proteins, cells can use biochemical networks to sense and process information. The differentiation of the cell state in colonic crypts forms a typical unidirectional phenotypic transitional cascade, in which stem cells differentiate into the transit-amplifying cells (TACs), and TACs continue to differentiate into fully differentiated cells. In order to quantitatively describe the relationship between the noise of each compartment and the amplification of signals, the gain factor is introduced, and the gain-fluctuation relation is obtained by using the linear noise approximation of the master equation. Through the simulation of these theoretical formulas, the characters of noise propagation and amplification are studied. It is found that the transmitted noise is an important part of the total noise in each downstream cell. Therefore, a small number of downstream cells can only cause its small inherent noise, but the total noise may be very large due to the transmitted noise. The influence of the transmitted noise may be the indirect cause of colon cancer. In addition, the total noise of the downstream cells always has a minimum value. As long as a reasonable value of the gain factor is selected, the number of cells in colonic crypts will be controlled within the normal range. This may be a good method to intervene the uncontrollable growth of tumor cells and effectively control the deterioration of colon cancer.