Hematopoietic stem cells (HSCs) can self-renew and differentiate to regenerate the hematopoietic system. While this regenerative potential is extensive, HSC function declines with successive rounds of divisions and increasing age. The molecular mechanisms for this decline remain mysterious and poorly understood. Our goal is to better define the molecular mechanisms that govern stemness and differentiation in the hematopoietic system and how these processes are altered in early stages of hematological diseases.