During development, HSCs emerge from the embryonic aorta and migrate to the fetal liver, a major hematopoietic site for their expansion and maturation. Fetal liver HSCs (FL-HSCs) are highly proliferative to ensure sustained production of functional blood cells, but also to generate the definitive pool of HSCs required to maintain adult hematopoiesis throughout life. Adult HSCs reside in the bone marrow (ABM-HSCs) and are predominantly quiescent (qHSCs), dividing only to maintain their numbers and generate multipotent (highly proliferative) progenitors. However, following stress, HSC proliferation is activated (aHSCs) in order to reconstitute the damaged blood system and/or to meet the needs of the immune system. Finally, over the years, the number of HSCs increases but their capacity for self-renewal decreases and their differentiation shifts towards the myeloid lineage; the incidence of hematological malignancies such as myeloproliferative disorders or myeloblastic leukemia increases with the appearance of leukemic stem cells (LSCs). In order to elucidate the mechanisms regulating the expansion/self-renewal (or even differentiation) of HSCs, we study HSCs in these different contexts HSC-FL, ABM-qHSC, ABM-aHSC and LSCs using mainly the mouse model (normal or transgenic).