Imaging the founder of adult hematopoiesis in the mouse embryo aorta

Hematopoietic stem cells (HSCs) are multipotent and capable of self-renewal. Therefore, HSCs can produce and replenish all blood cell types during the entire life, with no HSC pool depletion. HSCs are the key element for long-term clinical therapies in blood-related genetic diseases and leukemia. But HSC clinical use and fundamental research are impeded due to the limiting number of HSCs available in tissues. Moreover, HSCs are very difficult to maintain or expand ex vivo without loss of stem potential, and so far impossible to generate in vitro. Thus it is essential to identify the mechanisms controlling HSC commitment and fate to develop new strategies for in vitro HSC generation/ expansion and fate manipulation. Adult HSCs are mainly located in the bone marrow (BM) where they are in close contact to osteoblasts (endosteal niche) and vascular/perivascular cells (vascular niche). Such niches create a protective microenvironment against apoptotic and differentiation stimuli, and maintain the pool of HSCs quiescent. Adult HSCs are not generated in the BM but during embryonic development. There, HSCs will transit via several hematopoietic sites that offer a suitable microenvironment for HSC generation, survival and expansion. In mouse embryo, adult-type HSCs are first detected, starting at precise embryonic day (E)10.5, in the dorsal aorta of the AortaGonad-Mesonephros (AGM) region (as shown by transplantation into irradiated wild-type adult recipients). Slightly later, HSCs are also found in the yolk sac, as well as in the placenta and fetal liver, two important HSC reservoirs where the cells massively expand before to colonize the