A dynamical model of the regulatory network controlling lymphopoiesis

Due to the large number of diseases associated to a malfunction of the hematopoietic system, there is an interest in knowing the molecular mechanisms controlling the differentiation of blood cell lineages. However, the structure and dynamical properties of the underlying regulatory network controlling this process is not well understood. This manuscript presents a regulatory network of 81 nodes, representing several types of molecules that regulate each other during the process of lymphopoiesis. The regulatory interactions were inferred mostly from published experimental data. However, 15 out of 159 regulatory interactions are predictions arising from the present study. The network is modelled as a continuous dynamical system, in the form of a set of differential equations. The dynamical behaviour of the model describes the differentiation process from the common lymphocyte precursor (CLP) to several mature B and T cell types; namely, plasma cell (PC), cytotoxic T lymphocyte (CTL), T helper 1 (Th1), Th2, Th17, and T regulatory (Treg) cells. The model qualitatively recapitulates key cellular differentiation events, being able to represent the directional and branched nature of lymphopoiesis, going from a multipotent progenitor to fully differentiated cell types.