Thrombopoietin-mediated metabolic regulation in quiescent hematopoietic stem cells
Ayako Nakamura-Ishizu, MD, PhD
Professor, Tokyo Women’s Medical University
ishizu.ayako(at)twmu.ac.jp
Abstract
Hematopoietic stem cells (HSC) in the adult bone marrow (BM) are predominantly cell cycle dormant and proliferate and differentiate to replenish mature blood cells upon stress. The precise mechanism through which HSCs maintain cell cycle quiescence, especially in the context of metabolic regulation remains elusive. Among the various factors which influence HSC cell cycle fate, the cytokine thrombopoietin (Thpo) uniquely regulates self-renewal, differentiation and quiescence of HSCs. We have studied the effects of Thpo signaling on HSCs through administration of Thpo receptor agonist (Romiplostim) to wild-type mice and Thpo deficient mice (Cell Reports, 2018, Blood 2021). HSCs from Thpo deficient mice efficiently reverted to quiescence upon administration of Thpo receptor agonist. Furthermore, our data identified unique metabolic profiles in HSCs which survive Thpo deficiency. In this seminar, we will discuss the multifaceted roles of Thpo signaling in lineage-specific differentiation as well as HSC maintenance through metabolic alterations, especially focusing on mitochondrial metabolism.
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