Hematopoietic stem cells, which share with other stem cells of adult tissue
s the ability to maintain constant the number and diversity of differentiat
ed mature cells throughout adult life offer a fabulous system to analyze me
chanisms controlling cell proliferation and differentiation. Cytokines cont
rolling the differentiation of intermediate progenitors into mature cells o
f the various lineages have been characterized and have been widely used, i
n vitro as in vivo, to increase the output of differentiated cells. In cont
rast, despite significant technological advances molecular events associate
d with the stem cell decisions first to either self-renew or differentiate,
and then to irreversibly commit to one of the lymphoid or of the myeloid p
athways are still very badly understood. This is partly explained by the la
ck of reliable assays, particularly in humans, to assess stern cell activit
y, and by the difficulty to dissect the composition of molecular complexes
regulating gene expression in these very rare cells. Despite these limitati
ons, recent evidence suggests that there is some flexibility in the initial
decisions of stem cells, and that extracellular factors may influence sten
t cell fate. If this is confirmed, it may then become possible to propose n
ew therapeutic strategies based on the manipulation of stem cell properties
.