Energy Landscapes for Early T Cell Development

Abstract: T cell lineage development from an early thymic progenitor involves programmed shutoff of progenitor gene expression, upregulation of T cell specification genes, and proliferation. This biological system has been deeply studied and a gene regulatory network (GRN) that can accurately describe the system has been presented. Such a GRN offers an excellent opportunity to study lineage commitment from a multipotent progenitor. In this work, we investigated the GRN governing early T cell development by considering cell commitment as movements in an energy landscape. Our energy landscape method provided predictions that are consistent with experimental observations, both with and without simulated gene knockdowns. Moreover, we implemented cell development and proliferation within the energy landscape framework. We were able to show the impact of noise levels on cell developmental speed. The results are coherent with what would be expected for realistic biological systems.