1028 - MITOCHONDRIA METABOLISM IN QUIESCENT AND CYCLING HEMATOPOIETIC STEM CELLS

Abstract

Cellular metabolism is an area of recent intense research interest. However, the metabolic requirements for adaptations of stem cells to their niches remain largely unaddressed. The cell metabolism may be quite different in quiescent and cycling HSCs. Most of the hematopoietic stem cells (HSCs) within the bone marrow show quiescent state. By contrast, upon stress hematopoiesis, HSCs actively divide to regenerate hematopoietic system with the appropriate balance between self-renewal and differentiation divisions. Here we have compared mitochondrial metabolism between the quiescent state and cycling state in various conditions. First, we will show that suppression of Ca2+ influx and subsequent mitochondrial membrane potential contributes to the maintenance of HSCs by slowing cell divisions. Next, under the stress hematopoiesis such as thrombopoietin (Thpo) administration or oppositely, in Thpo-deficient mice, cell metabolism is drastically changed accompanying by the shift of the HSC subpopulation. Finally, using ATG7-deficient mice, we want to suggest that autophagy process is involved in the maintaining quiescence in adult HSCs, but not in neonatal HSCs, which show different nature in cell metabolism from that of adult quiescent HSCs. We will clarify the common and different points of cycling neonatal and dormant adult HSCs, as well as Thpo-deficient HSCs. Then, we would like to propose two types (dormant and cycling) of self-renewing HSCs.