We have applied the logical modelling framework to the regulatory network controlling T-lymphocyte specification. This process involves cross-regulations between specific T-cell regulatory factors with factors driving alternative differentiation pathways, which remain accessible during the early steps of thymocyte development. Many transcription factors needed for T-cell specification are required in other hematopoietic differentiation pathways, and are combined in a fine-tuned, time-dependent fashion to achieve T-cell commitment.
Using the software GINsim, we integrated current knowledge into a dynamical model, which recapitulates the main developmental steps from early progenitors entering the thymus up to T-cell commitment, as well as the impact of various documented environmental and genetic perturbations. Our model analysis further enabled the identification of several knowledge gaps.
The associated notebook can be loaded using the CoLoMoTo notebook docker image (see http://www.colomoto.org/notebook).
Jupyter Notebook: Tdev_notebook_2nov2019.ipynb