**5. Conclusion**

In this chapter, I have summarized our current knowledge regarding the hypoxia response and oxygen metabolism in HSCs at the BM niche. These studies open novel fields in stem cell biology. The invisible niche factor, oxygen, is usually essential because mitochondria utilize it for the energy production. However, molecular oxygen is a source of ROS during mitochondrial metabolism. Because an excessive dose of ROS can be damaging to HSC, escape from oxygen (in the hypoxic niche) is a reasonable strategy for the long-term maintenance of HSCs *in vivo*. Adult HSCs are quiescent and contain few mitochondria, whereas hematopoietic progenitor cells actively proliferate and contain many mitochondria. Thus, stem cells and progenitors have distinct metabolic states, and the transition from stem to progenitor cell may correspond to a critical metabolic change, namely from glycolysis to oxidative phosphorylation. Slow cell cycling or long-term quiescence is common in adult tissue stem cells. Dormancy in the cell cycle may be a crucial mechanism for the stress resistance of normal and leukemic stem cells.

Further investigation of oxygen metabolism in tissue stem cells will result in more effective maintenance, expansion, and manipulation of various somatic stem cells *ex vivo* and *in vivo*, maximizing the potential of therapeutic strategies using stem cells in regenerative medicine. Also, an understanding of oxygen homeostasis in HSCs is essential for understanding senescence at the stem cell level as well as therapeutic targeting against leukemic stem cells.
