{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,21]],"date-time":"2026-05-21T06:54:24Z","timestamp":1779346464465,"version":"3.51.4"},"reference-count":26,"publisher":"Oxford University Press (OUP)","issue":"12","license":[{"start":{"date-parts":[[2021,11,19]],"date-time":"2021-11-19T00:00:00Z","timestamp":1637280000000},"content-version":"vor","delay-in-days":769,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2019,10,12]],"date-time":"2019-10-12T00:00:00Z","timestamp":1570838400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2019,10,12]],"date-time":"2019-10-12T00:00:00Z","timestamp":1570838400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["1074"],"award-info":[{"award-number":["1074"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["1279"],"award-info":[{"award-number":["1279"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["1789"],"award-info":[{"award-number":["1789"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["1074"],"award-info":[{"award-number":["1074"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["1279"],"award-info":[{"award-number":["1279"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["1789"],"award-info":[{"award-number":["1789"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2019,12,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>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 \u00a02019;37:1606\u20131614<\/jats:p>\n               <jats:sec>\n                  <jats:title\/>\n               <\/jats:sec>","DOI":"10.1002\/stem.3087","type":"journal-article","created":{"date-parts":[[2019,10,1]],"date-time":"2019-10-01T16:21:16Z","timestamp":1569946876000},"page":"1606-1614","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["HPRT and Purine Salvaging Are Critical for Hematopoietic Stem Cell Function"],"prefix":"10.1093","volume":"37","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7687-516X","authenticated-orcid":false,"given":"Mona","family":"Vogel","sequence":"first","affiliation":[{"name":"a Institute of Molecular Medicine, Ulm University, Ulm, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bettina","family":"Moehrle","sequence":"additional","affiliation":[{"name":"a Institute of Molecular Medicine, Ulm University, Ulm, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andreas","family":"Brown","sequence":"additional","affiliation":[{"name":"a Institute of Molecular Medicine, Ulm University, Ulm, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Karina","family":"Eiwen","sequence":"additional","affiliation":[{"name":"a Institute of Molecular Medicine, Ulm University, Ulm, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vadim","family":"Sakk","sequence":"additional","affiliation":[{"name":"a Institute of Molecular Medicine, Ulm University, Ulm, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hartmut","family":"Geiger","sequence":"additional","affiliation":[{"name":"a Institute of Molecular Medicine, Ulm University, Ulm, Germany"},{"name":"b Division of Experimental Hematology and Cancer Biology, Cincinnati Children\u2019s Hospital Medical Center and University of Cincinnati, Cincinnati, Ohio, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2019,10,12]]},"reference":[{"key":"2022022515042997600_stem3087-bib-0001","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1146\/annurev-cellbio-111315-125134","article-title":"Metabolism and the control of cell fate decisions and stem cell renewal","volume":"32","author":"Ito","year":"2016","journal-title":"Annu Rev Cell Dev Biol"},{"key":"2022022515042997600_stem3087-bib-0002","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1016\/j.cmet.2006.02.002","article-title":"HIF-1-mediated expression of pyruvate dehydrogenase kinase: A metabolic switch required for cellular adaptation to hypoxia","volume":"3","author":"Kim","year":"2006","journal-title":"Cell Metab"},{"key":"2022022515042997600_stem3087-bib-0003","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1016\/j.stem.2010.06.020","article-title":"Regulation of the HIF-1\u03b1 level is essential for hematopoietic stem cells","volume":"7","author":"Takubo","year":"2010","journal-title":"Cell Stem Cell"},{"key":"2022022515042997600_stem3087-bib-0004","doi-asserted-by":"crossref","first-page":"380","DOI":"10.1016\/j.stem.2010.07.011","article-title":"The distinct metabolic profile of hematopoietic stem cells reflects their location in a hypoxic niche","volume":"7","author":"Simsek","year":"2010","journal-title":"Cell Stem Cell"},{"key":"2022022515042997600_stem3087-bib-0005","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1016\/j.stem.2012.10.011","article-title":"Regulation of glycolysis by Pdk functions as a metabolic checkpoint for cell cycle quiescence in hematopoietic stem cells","volume":"12","author":"Takubo","year":"2013","journal-title":"Cell Stem Cell"},{"key":"2022022515042997600_stem3087-bib-0006","doi-asserted-by":"crossref","first-page":"2535","DOI":"10.1242\/dev.091777","article-title":"Stem cell metabolism in tissue development and aging","volume":"140","author":"Shyh-Chang","year":"2013","journal-title":"Development"},{"key":"2022022515042997600_stem3087-bib-0007","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1016\/j.stem.2016.05.013","article-title":"p38\u03b1 activates purine metabolism to initiate hematopoietic stem\/progenitor cell cycling in response to stress","volume":"19","author":"Karigane","year":"2016","journal-title":"Cell Stem Cell"},{"key":"2022022515042997600_stem3087-bib-0008","doi-asserted-by":"crossref","first-page":"9431","DOI":"10.3390\/ijms16059431","article-title":"Nucleotide salvage deficiencies, DNA damage and neurodegeneration","volume":"16","author":"Fasullo","year":"2015","journal-title":"Int J Mol Sci"},{"key":"2022022515042997600_stem3087-bib-0009","doi-asserted-by":"crossref","first-page":"2466","DOI":"10.1093\/nar\/gkv047","article-title":"Regulation of mammalian nucleotide metabolism and biosynthesis","volume":"43","author":"Lane","year":"2015","journal-title":"Nucleic Acids Res"},{"key":"2022022515042997600_stem3087-bib-0010","first-page":"2475","article-title":"Enzymic capacities of purine de novo and salvage pathways for nucleotide synthesis in normal and neoplastic tissues","volume":"44","author":"Natsumeda","year":"1984","journal-title":"Cancer Res"},{"key":"2022022515042997600_stem3087-bib-0011","doi-asserted-by":"crossref","first-page":"17719","DOI":"10.1074\/jbc.272.28.17719","article-title":"Amidophosphoribosyltransferase limits the rate of cell growth-linked de novo purine biosynthesis in the presence of constant capacity of salvage purine biosynthesis","volume":"272","author":"Yamaoka","year":"1997","journal-title":"J Biol Chem"},{"key":"2022022515042997600_stem3087-bib-0012","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1093\/oxfordjournals.jbchem.a022730","article-title":"The rate of cell growth is regulated by purine biosynthesis via ATP production and G(1) to S phase transition","volume":"128","author":"Kondo","year":"2000","journal-title":"J Biochem (Tokyo)"},{"key":"2022022515042997600_stem3087-bib-0013","doi-asserted-by":"crossref","first-page":"21285","DOI":"10.1074\/jbc.M011103200","article-title":"Feedback inhibition of amidophosphoribosyltransferase regulates the rate of cell growth via purine nucleotide, DNA, and protein syntheses","volume":"276","author":"Yamaoka","year":"2001","journal-title":"J Biol Chem"},{"key":"2022022515042997600_stem3087-bib-0014","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1146\/annurev.ge.19.120185.001015","article-title":"HPRT: Gene structure, expression, and mutation","volume":"19","author":"Stout","year":"1985","journal-title":"Annu Rev Genet"},{"key":"2022022515042997600_stem3087-bib-0015","doi-asserted-by":"crossref","first-page":"6763","DOI":"10.1093\/nar\/10.21.6763","article-title":"Hypoxanthine-guanine phosphoribosyltransferase genes of mouse and Chinese hamster: Construction and sequence analysis of cDNA recombinants","volume":"10","author":"Konecki","year":"1982","journal-title":"Nucleic Acids Res"},{"key":"2022022515042997600_stem3087-bib-0016","doi-asserted-by":"crossref","first-page":"D1034","DOI":"10.1093\/nar\/gks1021","article-title":"HemaExplorer: A database of mRNA expression profiles in normal and malignant haematopoiesis","volume":"41","author":"Bagger","year":"2013","journal-title":"Nucleic Acids Res"},{"key":"2022022515042997600_stem3087-bib-0017","doi-asserted-by":"crossref","first-page":"2412","DOI":"10.1016\/j.celrep.2015.11.030","article-title":"Stem cell specific mechanisms ensure genomic fidelity within HSCs and upon aging of HSCs","volume":"13","author":"Moehrle","year":"2015","journal-title":"Cell Rep"},{"key":"2022022515042997600_stem3087-bib-0018","doi-asserted-by":"crossref","first-page":"2036","DOI":"10.1111\/j.1471-4159.1993.tb03488.x","article-title":"Brain purines in a genetic mouse model of Lesch-Nyhan disease","volume":"60","author":"Jinnah","year":"1993","journal-title":"J Neurochem"},{"key":"2022022515042997600_stem3087-bib-0019","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1038\/ng0393-235","article-title":"Production of a model for Lesch-Nyhan syndrome in hypoxanthine phosphoribosyltransferase-deficient mice","volume":"3","author":"Wu","year":"1993","journal-title":"Nat Genet"},{"key":"2022022515042997600_stem3087-bib-0020","doi-asserted-by":"crossref","first-page":"570","DOI":"10.1016\/j.ymgme.2015.02.007","article-title":"Consequences of impaired purine recycling on the proteome in a cellular model of lesch-nyhan disease","volume":"114","author":"Dammer","year":"2015","journal-title":"Mol Genet Metab"},{"key":"2022022515042997600_stem3087-bib-0021","doi-asserted-by":"crossref","first-page":"805","DOI":"10.1111\/jnc.12366","article-title":"Purine metabolism during neuronal differentiation: The relevance of purine synthesis and recycling","volume":"127","author":"G\u00f6ttle","year":"2013","journal-title":"J Neurochem"},{"key":"2022022515042997600_stem3087-bib-0022","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1007\/BF00485961","article-title":"Lesch-Nyhan syndrome: Absence of the mutant enzyme in erythrocytes of heterozygote for both normal and mutant hypoxanthine-guanine phosphoribosyl transferase","volume":"6","author":"McDonald","year":"1972","journal-title":"Biochem Genet"},{"key":"2022022515042997600_stem3087-bib-0023","doi-asserted-by":"crossref","first-page":"859","DOI":"10.1242\/dev.118.3.859","article-title":"Age-dependent selection against hypoxanthine phosphoribosyl transferase-deficient cells in mouse haematopoiesis","volume":"118","author":"Samuel","year":"1993","journal-title":"Development"},{"key":"2022022515042997600_stem3087-bib-0024","doi-asserted-by":"crossref","first-page":"500","DOI":"10.1002\/jnr.1044","article-title":"Hypoxanthine impairs morphogenesis and enhances proliferation of a neuroblastoma model of Lesch Nyhan syndrome","volume":"63","author":"Ma","year":"2001","journal-title":"J Neurosci Res"},{"key":"2022022515042997600_stem3087-bib-0025","doi-asserted-by":"crossref","first-page":"538","DOI":"10.1097\/FJC.0b013e318271223c","article-title":"Xanthine oxidase contributes to mitochondrial ros generation in an experimental model of cocaine-induced diastolic dysfunction","volume":"60","author":"Vergeade","year":"2012","journal-title":"J Cardiovasc Pharmacol"},{"key":"2022022515042997600_stem3087-bib-0026","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0059594","article-title":"Knockdown of HPRT for selection of genetically modified human hematopoietic progenitor cells","volume":"8","author":"Choudhary","year":"2013","journal-title":"PLoS One"}],"container-title":["Stem Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fstem.3087","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/stem.3087","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/stem.3087","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/academic.oup.com\/stmcls\/article-pdf\/37\/12\/1606\/42612146\/stmcls_37_12_1606.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/stmcls\/article-pdf\/37\/12\/1606\/42612146\/stmcls_37_12_1606.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,2,25]],"date-time":"2022-02-25T15:24:50Z","timestamp":1645802690000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/stmcls\/article\/37\/12\/1606\/6430734"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,10,12]]},"references-count":26,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2019,10,12]]},"published-print":{"date-parts":[[2019,12,1]]}},"URL":"https:\/\/doi.org\/10.1002\/stem.3087","relation":{},"ISSN":["1066-5099","1549-4918"],"issn-type":[{"value":"1066-5099","type":"print"},{"value":"1549-4918","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2019,12,1]]},"published":{"date-parts":[[2019,10,12]]},"assertion":[{"value":"2019-04-24","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-08-23","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-10-12","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}