Effect of dedifferentiation on noise propagation in cellular hierarchy

Many fast renewing tissues have a hierarchical structure. Tissue-specific stem cells are at the root of this cellular hierarchy, which give rive to a whole range of specialized cells via cellular differentiation. However, increasing evidence shows that the hierarchical structure can be broken due to cellular dedifferentiation in which cells at differentiated stages can revert to the stem cell stage. Dedifferentiation has significant impacts on many aspects of hierarchical tissues. Here we investigate the effect of dedifferentiation on noise propagation by developing a stochastic model composed of different cell types. The moment equations are derived, via which we systematically investigate how the noise in the cell number is changed by dedifferentiation. Our results suggest that dedifferentiation have different effects on the noises in the numbers of stem cells and nonstem cells. Specifically, the noise in the number of stem cells is significantly reduced by increasing dedifferentiation probability. Due to the dual effect of dedifferentiation on nonstem cells, however, more complex changes could happen to the noise in the number of nonstem cells by increasing dedifferentiation probability. Furthermore, it is found that even though dedifferentiation could turn part of the noise propagation process into a noise-amplifying step, it is very unlikely to turn the entire process into a noise-amplifying cascade.