Date: April 19, 2018. 12:00
Location: CCU Seminar Room
Title: Cell competition in the thymus and Leukemia.
Affiliation: Instituto Gulbenkian de Ciência, Portugal.
Most T lymphocyte development occurs in the thymus from progenitors of bone marrow origin in a process characterized by high cellular turnover. We found that thymus turnover is regulated by cell competition. During T lymphocyte development, cell competition occurs at a specific stage of differentiation. At that stage, precursors differ slightly in their time of thymus residency. Specifically, ‘young’ hematopoietic precursors (that recently seeded the thymus) coexist with ‘old’ precursors (residing for longer in the thymus). These cells share the same surface markers that identify them as sharing the same differentiation stage, but young precursors induce the clearance of the old, thereby promoting thymus turnover. This is a particularly dynamic process, as winner cells progressively differentiate into more mature stages. Impairment or disruption of cell competition is permissive to self-renewal and persistence of the old precursors. These maintain thymus function autonomously for some weeks with de novo production and export of T lymphocytes. However, prolongation of this property invariably leads to development of T cell acute lymphoblastic leukemia (T-ALL) with strong similarities to the human disease. We identified the intra-thymic populations at which cell competition takes place. Moreover, we found that a small population of T lymphocyte precursors persists long-term in the thymus, while maintaining thymus function autonomously. Finally, we show that thymus autonomy invariably leads to T-ALL.