The nucleotide sugar UDP-glucose mobilizes long-term repopulating primitive hematopoietic cells
Open Access
- 25 July 2013
- journal article
- Published by American Society for Clinical Investigation in JCI Insight
- Vol. 123 (8), 3420-3435
- https://doi.org/10.1172/jci64060
Abstract
Hematopoietic stem progenitor cells (HSPCs) are present in very small numbers in the circulating blood in steady-state conditions. In response to stress or injury, HSPCs are primed to migrate out of their niche to peripheral blood. Mobilized HSPCs are now commonly used as stem cell sources due to faster engraftment and reduced risk of posttransplant infection. In this study, we demonstrated that a nucleotide sugar, UDP-glucose, which is released into extracellular fluids in response to stress, mediates HSPC mobilization. UDP-glucose–mobilized cells possessed the capacity to achieve long-term repopulation in lethally irradiated animals and the ability to differentiate into multi-lineage blood cells. Compared with G-CSF–mobilized cells, UDP-glucose–mobilized cells preferentially supported long-term repopulation and exhibited lymphoid-biased differentiation, suggesting that UDP-glucose triggers the mobilization of functionally distinct subsets of HSPCs. Furthermore, co-administration of UDP-glucose and G-CSF led to greater HSPC mobilization than G-CSF alone. Administration of the antioxidant agent NAC significantly reduced UDP-glucose–induced mobilization, coinciding with a reduction in RANKL and osteoclastogenesis. These findings provide direct evidence demonstrating a potential role for UDP-glucose in HSPC mobilization and may provide an attractive strategy to improve the yield of stem cells in poor-mobilizing allogeneic or autologous donors.Keywords
This publication has 68 references indexed in Scilit:
- Osteoclasts are dispensable for hematopoietic stem cell maintenance and mobilizationThe Journal of Experimental Medicine, 2011
- Sox17 expression confers self-renewal potential and fetal stem cell characteristics upon adult hematopoietic progenitorsGenes & Development, 2011
- Genomic and Proteomic Analysis of the Impact of Mitotic Quiescence on the Engraftment of Human CD34+ CellsPLOS ONE, 2011
- Osteoclast Response to Low Extracellular Sodium and the Mechanism of Hyponatremia-induced Bone LossPublished by Elsevier BV ,2011
- Ewing sarcoma gene Ews regulates hematopoietic stem cell senescenceBlood, 2011
- Hematopoietic stem and progenitor cells are differentially mobilized depending on the duration of Flt3-ligand administrationHaematologica, 2010
- The UDP-Glucose Receptor P2RY14 Triggers Innate Mucosal Immunity in the Female Reproductive Tract by Inducing IL-8The Journal of Immunology, 2009
- The inflammatory effects of UDP-glucose in N9 microglia are not mediated by P2Y14 receptor activationPurinergic Signalling, 2008
- UDP Is a Competitive Antagonist at the Human P2Y14ReceptorThe Journal of pharmacology and experimental therapeutics, 2008
- Structure−Activity Relationship of Uridine 5‘-Diphosphoglucose Analogues as Agonists of the Human P2Y14 ReceptorJournal of Medicinal Chemistry, 2007