T-lymphocyte specification

Taxon: Mammal
Process: Differentiation | Signalling | Development
Submitter: Pedro Monteiro

Supporting paper: Cacace, Elisabetta and Collombet, Samuel and Thieffry, Denis (2020). Logical modeling of cell fate specification-Application to T cell commitment. . 10.1016/bs.ctdb.2020.02.008

Model file(s)	Description(s)
Cacace_Tdev_2nov2019.zginml	GINsim model file
Cacace_TdevModel_SBML_2nov2019.sbml	SBML model file
Tdev_notebook_2nov2019.ipynb	Jupyter notebook using the CoLoMoTo environment

Summary:
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.