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Stem Cells. 2019 Dec;37(12):1606-1614. doi: 10.1002/stem.3087. Epub 2019 Oct 12.

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

Author information

1
Institute of Molecular Medicine, Ulm University, Ulm, Germany.
2
Division of Experimental Hematology and Cancer Biology, Cincinnati Children's Hospital Medical Center and University of Cincinnati, Cincinnati, Ohio, USA.

Abstract

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.

KEYWORDS:

HPRT-associated purine salvaging; Hematopoietic stem and progenitor cells (HSPCs); Mitochondria function; Proliferation kinetics; Purine nucleotide metabolism

PMID:
31574190
DOI:
10.1002/stem.3087

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