Hematopoietic stem cells (HSCs) are rare cells located in the bone marrow, which are ultimately responsible for the lifelong generation of all blood cell types. In essence, HSCs ensure these processes by both being able to self-renew, thereby maintaining an adequate pool of HSCs from which differentiation can commence, as well as via tightly regulated differentiation processes, in which the progeny of HSCs become increasingly restricted with regards to differential potential to finally become “locked” to one specific cell lineage. A broader interest of our laboratory is therefore to understand the molecular regulation of HSCs both from the perspectives of self-renewal and differentiation, and how these features become altered upon disease-causing or disease-associated perturbations.