Insights into signaling and function of hematopoietic stem cells at the single-cell level

Abstract

Development of a technique prospectively to isolate hematopoietic stem cells (HSCs) to near homogeneity has enabled clonal analysis and thus converted our understanding of HSCs from conceptual and qualitative to realistic and quantitative. Recent studies have revealed that despite their high proliferation potential, most HSCs are in G0 and enter cell cycle only after a long interval. This dormancy of HSCs, which seems to be important for long-term maintenance of 'stemness', appears to be regulated by the exchange of signals between HSCs and the bone marrow niche. Analysis of intersignaling and intrasignaling events in HSCs in and out of the bone marrow niche has begun. With the help of advances in confocal microscopy, laser scanning microscopy, and personal computer computational power over the last decade, it has become evident that thrombopoietin/c-Mpl signaling plays a role in HSC self-renewal and AKT-forkhead box O signaling in HSC dormancy. Furthermore, transforming growth factor-beta has been indicated as a candidate niche signal to induce hibernation in HSCs. Understanding of the signaling events between HSCs and niche is critical not only for stem cell biology in general and for transplantation medicine but also for the development of novel cancer therapy.