Enhancing the Generation of Progenitor T-cells from Hematopoietic Stem Cells

T-cells are an essential component of the adaptive immune system that responds to pathogens and provides surveillance against cancerous cells. In vivo, T-cells develop from hematopoietic stem cells (HSCs) in a specialized organ called the thymus that provides unique and stage specific cues to developing T-cell progenitor (proT) cells. The development of robust in vitro systems for generating proT-cells from HSCs would enable new clinical therapies for treating cancer and immunological disorders. Current assays that are amenable for clinical translation are inefficient and do not generate cells in sufficient quantities for therapeutic use. I hypothesized that incorporating molecules present in the thymus into in vitro assays would better recapitulate development and improve proT-cell generation. I identified synergistic effects between inflammatory cytokines and showed that this effect is mediated through the positive regulation of T-lineage developmental genes. This work provides new strategies for engineering systems for generating proT-cells for clinical therapies.M.A.S.2019-11-15 00:00:0