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Publication : HPRT and Purine Salvaging Are Critical for Hematopoietic Stem Cell Function.

First Author  Vogel M Year  2019
Journal  Stem Cells Volume  37
Issue  12 Pages  1606-1614
PubMed ID  31574190 Mgi Jnum  J:294102
Mgi Id  MGI:6446413 Doi  10.1002/stem.3087
Citation  Vogel M, et al. (2019) HPRT and Purine Salvaging Are Critical for Hematopoietic Stem Cell Function. Stem Cells 37(12):1606-1614
abstractText  Adult hematopoietic stem cells (HSCs) maintain tissue homeostasis and regenerative capacity of the hematopoietic system through self-renewal and differentiation. Metabolism is recognized as an important regulatory entity controlling stem cells. As purine nucleotides are essential for metabolic functions, we analyzed the role of hypoxanthine guanine phosphoribosyl transferase (HPRT)-associated purine salvaging in HSCs. Here, we demonstrate that hematopoietic stem and progenitor cells (HSPCs) show a strong dependence on HPRT-associated purine salvaging. HSPCs with lower HPRT activity had a severely reduced competitive repopulation ability upon transplantation. Strikingly, HPRT deficiency resulted in altered cell-cycle progression, proliferation kinetics and mitochondrial membrane potential primarily in the HSC compartment, whereas more committed progenitors were less affected. Our data thus imply a unique and important role of HPRT and the purine salvage pathway for HSC function. Stem Cells 2019;37:1606-1614.
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