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The nucleotide sugar UDP-glucose mobilizes long-term repopulating primitive hematopoietic cells
Sungho Kook, … , Sean Bong Lee, Byeong-Chel Lee
Sungho Kook, … , Sean Bong Lee, Byeong-Chel Lee
Published July 25, 2013
Citation Information: J Clin Invest. 2013;123(8):3420-3435. https://doi.org/10.1172/JCI64060.
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Research Article Hematology

The nucleotide sugar UDP-glucose mobilizes long-term repopulating primitive hematopoietic cells

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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.

Authors

Sungho Kook, Joonseok Cho, Sean Bong Lee, Byeong-Chel Lee

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Figure 8

NAC abrogates UDP-Glc–induced mobilization.

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NAC abrogates UDP-Glc–induced mobilization.
(A and B) Mice (n > 4/gro...
(A and B) Mice (n > 4/group) were treated with NAC as described in the Methods. UDP-Glc–mediated LSK (A) and SLAM LSK (B) cell mobilization was significantly suppressed by NAC treatment. The data shown are the mean ± SD. (C and D) Mice were treated as described in A. RANKL expression was determined with Western blotting (C) and immunohistochemistry (D). In Western blot analysis, the numerical values represent the fold change in densitometry data (calculated as described above). Scale bar: 50 μM. (E) Mice were treated as indicated. Arrowheads indicate TRAP-positive cells. A representative TRAP staining is shown. Scale bar: 50 μM. #P < 0.05, ##P < 0.01, **P < 0.01.

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