HPRT and Purine Salvaging Are Critical for Hematopoietic Stem Cell Function

Authors:
Open Access
Publisher website
Google Scholar
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. © AlphaMed Press 2019 Significance Statement Metabolism controls stem cell function. Purine metabolism is a critical component of cellular metabolism. Here, we report that a reduced activity of the purine salvaging enzyme HPRT in HSCs (HPRTlow HSCs) result in reduced fitness of HSCs and alters their cell cycle profile and the function of their mitochondria. Our data suggest that this phenotype of HPRTlow HSCs is due to elevated levels of purine degradation rather than a lack of purine recycling, implying an important role for HPRT mediated purine salvaging for HSC function.
Funding Information
  • Deutsche Forschungsgemeinschaft (1074, 1279, 1789)
  • Deutsche Forschungsgemeinschaft (1074, 1279, 1789)

This publication has 25 references indexed in Scilit: