Stem cells are capable of both generating identical progeny, and producing transit amplifying cells (TA-cells) committed to differentiate. Regulation of the number of stem cells, TA-cells and differentiated cells is a crucial problem in multicellular organisms. Defects in stem cell renewal may lead to lineage disappearance or cancer. Many of the features that govern the behavior of stem cells remain unknown. Our research is directed towards understanding what drives stem cell emergence, maintenance, and differentiation of their TA-cells progeny. We are using genetic approaches in the mouse to address these issues in an in vivo context. We focus our research on Notchless, which our lab has discovered as an important regulator of stem cells maintenance. Our aim is to decipher the cellular behaviours and molecular mechanisms underlying Notchless function in stem cells using three main paradigms: embryonic stem cells, the haematopoietic system and the gut epithelium.