Every day about 1 trillion new blood cells are formed, of which the majority are red blood cells. This depends on a small number of hematopoietic stem cells that are able to both self-renew to maintain the stem cell pool, and to mature into all types of mature blood cells. Anemia is associated with aging, chronic infections and cancer, and significantly impacts quality of life and survival. It is primarily treated with blood transfusions or injections of Erythropoietin (EPO). However, repeated transfusions result in iron overload with severe side effects, and many forms of anemia do not respond well to EPO treatment. It is therefore important to find new ways to enhance red blood cell production. The aim of our research is to derive conceptually novel mechanisms to treat anemia with the goal to improve quality of life and survival of patients, as well as to understand how chronic anemia affects the ability of hematopoietic stem cells to provide balanced long-term blood production.