Open AccessHPRT and Purine Salvaging Are Critical for Hematopoietic Stem Cell Function
Author(s) -
Vogel Mona,
Moehrle Bettina,
Brown Andreas,
Eiwen Karina,
Sakk Vadim,
Geiger Hartmut
Publication year - 2019
Publication title -
stem cells
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.159
H-Index - 229
eISSN - 1549-4918
pISSN - 1066-5099
DOI - 10.1002/stem.3087
Subject(s) - biology , haematopoiesis , stem cell , hypoxanthine guanine phosphoribosyltransferase , microbiology and biotechnology , progenitor cell , hypoxanthine , hematopoietic stem cell , biochemistry , enzyme , mutant , gene
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