Hematopoietic stem cells (HSCs) are capable of self-renewal and multi-lineage differentiation. The fate of HSCs is determined by the intrinsic cell program and the extrinsic microenvironment (niche) effect. Conceptually, the number of HSCs is determined by the probability of self-renewal division occurring through symmetrical and/or asymmetrical divisions under the influence of niche. Although self-renewal is essential for maintaining HSCs, the mechanism of the process has not been well elucidated and the ex vivo expansion of HSCs remains challenging.

Our work on HSCs encompass the purification of HSCs, identification of cytokine signaling in hematopoiesis, and the characterization of HSC niches in the bone marrow. We have delineated the endosteal and vascular niches for HSCs and have cultivated new fields of oxidative stress (ROS) and stem cell aging.

During step-wise differentiation of stem cells, the metabolic state associated with each differentiation stage differs. We have shown that quiescent HSCs predominantly utilize glycolytic pathways under the control of hypoxia inducible factor (HIF) 1-alpha, while proliferating HSCs obtain energy through oxidative phosphorylation and purinergic metabolism.

Cellular metabolism is an area of intense research interest. However, the metabolic requirements and adaptations of stem cells and their niches remain largely unaddressed. I would like to summarize our recent works on HSC metabolism, which suggest that appropriate regulations of the metabolic state of HSCs may allow HSCs to self-renew and expand.