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AuthorVogel, Monadc.contributor.author
AuthorMöhrle, Bettina Mariadc.contributor.author
AuthorBrown, Andreasdc.contributor.author
AuthorEiwen, Karinadc.contributor.author
AuthorSakk, Vadimdc.contributor.author
AuthorGeiger, Hartmutdc.contributor.author
Date of accession2021-11-29T12:59:08Zdc.date.accessioned
Available in OPARU since2021-11-29T12:59:08Zdc.date.available
Date of first publication2019-10-01dc.date.issued
AbstractAdult 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;37:1606–1614dc.description.abstract
AbstractFree purine bases are recycled by the purine salvaging enzyme hypoxanthine guanine phosphoribosyl transferase (HPRT) (left). A reduced activity of HPRT alters cell‐cycle progression and function of mitochondria (right) in hematopoietic stem cells (HSCs), which is linked to reduced HSC repopulation ability upon transplantation. Our data suggest that an elevated level of purine degradation products might initiate these phenotypes in HSCs in which HPRT activity is reduced.dc.description.abstract
Languageendc.language.iso
PublisherUniversität Ulmdc.publisher
LicenseCC BY-NC 4.0 Internationaldc.rights
Link to license texthttps://creativecommons.org/licenses/by-nc/4.0/dc.rights.uri
KeywordHematopoietic stem and progenitor cells (HSPCs)dc.subject
KeywordPurine nucleotide metabolismdc.subject
KeywordHPRT-associated purine salvagingdc.subject
KeywordProliferation kineticsdc.subject
KeywordMitochondria functiondc.subject
Dewey Decimal GroupDDC 570 / Life sciencesdc.subject.ddc
Dewey Decimal GroupDDC 610 / Medicine & healthdc.subject.ddc
Dewey Decimal GroupDDC 620 / Engineering & allied operationsdc.subject.ddc
LCSHBiosynthesisdc.subject.lcsh
MeSHHematopoietic stem cellsdc.subject.mesh
MeSHStem cellsdc.subject.mesh
MeSHMitochondriadc.subject.mesh
MeSHCell cycledc.subject.mesh
MeSHNucleotidesdc.subject.mesh
MeSHDNAdc.subject.mesh
MeSHLesch-Nyhan Syndromedc.subject.mesh
TitleHPRT and purine salvaging are critical for hematopoietic stem cell functiondc.title
Resource typeWissenschaftlicher Artikeldc.type
SWORD Date2020-12-09T19:34:41Zdc.date.updated
VersionpublishedVersiondc.description.version
DOIhttp://dx.doi.org/10.18725/OPARU-40037dc.identifier.doi
URNhttp://nbn-resolving.de/urn:nbn:de:bsz:289-oparu-40113-8dc.identifier.urn
GNDBlutstammzelledc.subject.gnd
GNDNucleotidedc.subject.gnd
GNDDNSdc.subject.gnd
GNDLesch-Nyhan-Syndromdc.subject.gnd
InstitutionZentralinstitut für Biomedizinische Technik (ZIBMT)uulm.affiliationSpecific
Peer reviewjauulm.peerReview
DCMI TypeTextuulm.typeDCMI
CategoryPublikationenuulm.category
In cooperation withUniversity of Cincinnatiuulm.cooperation
DOI of original publication10.1002/stem.3087dc.relation1.doi
Source - Title of sourceStem Cellssource.title
Source - Place of publicationWileysource.publisher
Source - Volume37source.volume
Source - Issue12source.issue
Source - Year2019source.year
Source - From page1606source.fromPage
Source - To page1614source.toPage
Source - ISSN1066-5099source.identifier.issn
Source - eISSN1549-4918source.identifier.eissn
CommunityZentrale Einrichtungenuulm.community
Bibliographyuulmuulm.bibliographie
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Is Supplemented Byhttps://stemcellsjournals.onlinelibrary.wiley.com/action/downloadSupplement?doi=10.1002%2Fstem.3087&file=stem3087-sup-0002-FigureS1.tiffdc.relation.isSupplementedBy
Is Supplemented Byhttps://stemcellsjournals.onlinelibrary.wiley.com/action/downloadSupplement?doi=10.1002%2Fstem.3087&file=stem3087-sup-0003-FigureS2.tiffdc.relation.isSupplementedBy
DFG project uulmSFB 1074 / Experimentelle Modelle und klinische Translation bei Leukämien / DFG / 217328187uulm.projectDFG
DFG project uulmSFB 1279 / Nutzung des menschlichen Peptidoms für die Entwicklung neuer antimikrobieller und anti-Krebs Therapeutika / DFG / 316249678uulm.projectDFG
DFG project uulmGRK 1789 / CEMMA / Zelluläre und molekulare Mechanismen der Alterung / DFG / 194266605uulm.projectDFG


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