HPRT and Purine Salvaging Are Critical for Hematopoietic Stem Cell Function.
Stem Cells
; 37(12): 1606-1614, 2019 12.
Article
em En
| MEDLINE
| ID: mdl-31574190
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;371606-1614.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Nucleotídeos de Purina
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Purinas
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Células-Tronco Hematopoéticas
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Diferenciação Celular
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Hipoxantina Fosforribosiltransferase
Limite:
Animals
Idioma:
En
Revista:
Stem Cells
Ano de publicação:
2019
Tipo de documento:
Article
País de afiliação:
Alemanha