Regulation of Hematopoietic Stem Cell Dynamics by Molecular Niche Signaling

Abstract Millions of blood cells are produced throughout the lifetime of an individual by a rare pool of hematopoietic stem cells (HSCs). A combination of microenvironmental cues from the bone marrow and intrinsic signals from the HSC dictates its fate to remain quiescent, become active, differentiate, migrate, or regenerate. Recent advances using genetically modified mouse models and high-resolution real-time imaging have helped us to identify HSC niche components and the molecular signaling emanating from them. Multiple signaling pathways, depending on the dosage of growth factors/cytokines and cellular sources, synergize or antagonize to maintain the HSC dynamics in response to physiological cues. Even though increasing evidence suggests that primitive HSCs are maintained by multipotent immature mesenchymal stromal cells, given the fact that the HSC itself is dynamic and exists as subsets, it is more likely that different cellular sources are needed to provide unique and shared signals. This chapter discusses findings on how the niche-network maintains different states of HSCs by providing multiple inputs during homeostasis and under stress.