Numerous factors regulating Hematopoietic Stem Cells (HSC) function have been identified during the last decade thanks to mouse models. During my PhD, I showed that Notchless (Nle) is required for the maintenance of adult HSC. Ubiquitous inactivation of Nle in adult mouse induced the death of the mouse within 12 days, preceded by a rapid disappearance of HSC and multipotent progenitors. Following Nle inactivation, HSC entered cell cycle, suggesting that Nle is critical to maintain HSC quiescence. No increase in apoptosis was detected. Several transplantations approaches showed that Nle is cell-autonomously required in HSC. Altogether these results indicate that Nle is a new regulator of HSC maintenance, both in homeostasis and under stress conditions. Moreover, in vivo and ex vivo approaches suggest that Nle is dispensable for B cells and myeloid progenitors development and survival. Recent data showed that Nle ortholog in yeast is involved in ribosome biogenesis. Using murine ES cells, I showed that this role is conserved in mouse. Using hematopoietic cells labelling coupled with FISH on rRNA, I showed that Nle deletion induced defects in ribosome biogenesis in HSC and immature progenitor cells, but not in B cells. Altogether, this study suggests that ribosome biogenesis might be specifically regulated depending on cell type, and particularly in stem cells
