Notch Signaling in the Regulation of Hematopoietic Stem Cell

Understanding the signaling pathways that govern hematopoietic stem and progenitor cells (HSPCs) is fundamental to uncover their regulation and how this is skewed in hematological malignancies. Whether Notch is necessary for the regulation of mammalian HSPCs is still unclear. We therefore critically review the current literature on the role of Notch in HSPCs.

HSPCs have shown different requirements for Notch signals in vitro and in vivo and at different stages of differentiation. Additionally, bone marrow niche cells activate Notch signaling in HSPCs enhancing their regenerative and self-renewal capacity.

Despite the controversy, adequate levels of Notch signaling appear necessary to avoid the development of hematological malignancies. Contrary to early studies, recent research suggests that Notch signaling may play a role in homeostatic and regenerative hematopoiesis but further investigation is necessary to understand how it is regulated by the different ligand/receptor pairings and the molecular mechanisms that are triggered.