Blood stem cells are special cells in our body that produce all blood and immune cells throughout life. They are already used in life-saving treatments for leukemia, and their use is expanding to gene and cell therapies aimed at treating other cancers, genetic diseases, autoimmune disorders, and infections. However, these therapies are not available to many patients because suitable donors cannot always be found, and sometimes the number of stem cells available is too low. Attempts to overcome these limitations by creating blood stem cells in the laboratory from pluripotent stem cells led to generation of cells that look like blood stem cells, but that behave more like immature cells from early development and lack the full functionality needed for effective treatment. The FUN-HSC project aims to understand how blood stem cells mature during human development and to identify the key biological pathways that control this process.
During fetal development, blood stem cells mature in the liver, where they acquire the ability to produce all types of blood cells throughout life. By studying human embryonic and fetal tissues at single-cell resolution, we have identified several gene programs that change as blood stem cells mature. Building on this knowledge, the project will investigate how developing stem cells interact with their surrounding environment in the fetal liver. Using new laboratory models that recreate this environment, such as organoids and mouse transplantation models, we will test which signals are necessary for stem cell maturation. Ultimately, the goal is to reproduce these developmental signals in the laboratory so that stem cells created from pluripotent stem cells can mature into fully functional blood stem cells. By combining new insights into human blood stem cell biology with advanced genetic and tissue-engineering technologies, FUN-HSC aims to bring us closer to producing reliable blood stem cells for therapy, expanding their life-saving potential for many more patients.
