Abstract
The quiescent state is thought to be a characteristic property for the maintenance of hematopoietic stem cells (HSCs). Interaction of HSCs with their particular microenvironments, known as the stem cell niches, is critical for adult hematopoiesis in the bone marrow (BM). We demonstrate that quiescent HSCs adhere to the hypoxic endosteal niche through the Tie2/ Angiopoietin-1, mpl/thrombopoietin and/or N-cadherin.
During BM transplantation or after treatment with myeloablative agents, the quiescent HSCs enter the cell cycle and proliferate to supply progenitors of hematopoietic cells. Reactive oxygen species (ROS)induce the exit of HSCs from the niche, resulting in the exhaustion of HSCs. To reduce the generation of ROS from mitochondria, HSCs gain the energy from glycolytic pathway rather than from oxidative phosphrylation under the regulation of HIF1alpha. I will present the change of HSC behavior and metabolism in mutant mice with HIF1alpha or VHL and discuss about the similarities between normal stem cells and cancer stem cells from the aspect of cell metabolism.
