Cellular mechanisms of haematopoietic lineage commitment

Every blood stem cell in the body carries a unique pattern of gene activity that shifts dramatically during aging, infection, and the early stages of leukaemia—and this project will map those shifts cell by cell. The problem is that we do not understand why blood production falters in older people or why some stem cells turn cancerous while others do not. Current knowledge lumps all blood stem cells together, but they are not identical. This project uses advanced single-cell DNA sequencing to measure which genes are active in individual stem cells, then watches how those patterns change under stress hormones, in leukaemia-causing mutations, and in aged cells. If successful, this work will identify distinct types of blood-forming stem cells and reveal how their populations shift with age and stress. That could eventually lead to rational therapies that either boost healthy blood production after infection or blood loss, or suppress the mutant stem cells that drive leukaemia. This is fundamental science—no immediate clinical tool will emerge from this grant alone—but similar single-cell mapping efforts have already transformed how we understand immune responses and tumour evolution, making future targeted treatments possible.