Mechanisms of self-renewal in hematopoietic stem cells.

A large number of studies have shown that quiescence is essential for hematopoietic stem cells (HSCs) to maintain their number and function. Otherwise, HSCs are exhausted or damaged by various substances. We need to understand how the quiescent state is maintained in HSCs, how HSCs are driven into the cell cycle, and how HSCs return to the quiescent state. We also need to understand how cycling HSCs make the decision whether to self-renew. A number of molecules have been reported as candidate regulators of these events in HSCs. In this review, we focus on the HSC niche, the cytokine network, and associated transcription factors; and then discuss to what extent we can currently understand these critical issues in stem cell biology.