T-cells are an important cell type involved in our body’s immune responses, with roles ranging from killing cancer to eliminating infection agents such as viruses. If we can tailor them properly, T cells will have tremendous potential such as anti-cancer CAR-T therapy. Unfortunately, engineering T-cells is an inefficient process, as only small batches can be produced at a time which is associated with a high cost. This problem could be resolved by manufacturing large batches of T-cells directly from stem cells. However, T-cell development is very complex and not enough is known to robustly recapitulate this process.
This project deployed multiple single-cell omics approaches to model T-cell development in the human thymus. Through this model, the project team found that as T cells migrate through the thymus during their development/maturation process, multiple factors, such as sex, protein factors, other cell types, and even T cells, could influence the development trajectories. This work helped inform the team on how to scale stem cell differentiation into mature T cells and manipulate the immune system during aging and diseases.