000127743 001__ 127743
000127743 005__ 20240228140947.0
000127743 0247_ $$2doi$$a10.1038/nature14131
000127743 0247_ $$2pmid$$apmid:25707806
000127743 0247_ $$2ISSN$$a0028-0836
000127743 0247_ $$2ISSN$$a1476-4687
000127743 0247_ $$2altmetric$$aaltmetric:3709136
000127743 037__ $$aDKFZ-2017-03766
000127743 041__ $$aeng
000127743 082__ $$a070
000127743 1001_ $$0P:(DE-HGF)0$$aWalter, Dagmar$$b0$$eFirst author
000127743 245__ $$aExit from dormancy provokes DNA-damage-induced attrition in haematopoietic stem cells.
000127743 260__ $$aLondon [u.a.]$$bNature Publ. Group$$c2015
000127743 3367_ $$2DRIVER$$aarticle
000127743 3367_ $$2DataCite$$aOutput Types/Journal article
000127743 3367_ $$0PUB:(DE-HGF)16$$2PUB:(DE-HGF)$$aJournal Article$$bjournal$$mjournal$$s1508331520_31106
000127743 3367_ $$2BibTeX$$aARTICLE
000127743 3367_ $$2ORCID$$aJOURNAL_ARTICLE
000127743 3367_ $$00$$2EndNote$$aJournal Article
000127743 520__ $$aHaematopoietic stem cells (HSCs) are responsible for the lifelong production of blood cells. The accumulation of DNA damage in HSCs is a hallmark of ageing and is probably a major contributing factor in age-related tissue degeneration and malignant transformation. A number of accelerated ageing syndromes are associated with defective DNA repair and genomic instability, including the most common inherited bone marrow failure syndrome, Fanconi anaemia. However, the physiological source of DNA damage in HSCs from both normal and diseased individuals remains unclear. Here we show in mice that DNA damage is a direct consequence of inducing HSCs to exit their homeostatic quiescent state in response to conditions that model physiological stress, such as infection or chronic blood loss. Repeated activation of HSCs out of their dormant state provoked the attrition of normal HSCs and, in the case of mice with a non-functional Fanconi anaemia DNA repair pathway, led to a complete collapse of the haematopoietic system, which phenocopied the highly penetrant bone marrow failure seen in Fanconi anaemia patients. Our findings establish a novel link between physiological stress and DNA damage in normal HSCs and provide a mechanistic explanation for the universal accumulation of DNA damage in HSCs during ageing and the accelerated failure of the haematopoietic system in Fanconi anaemia patients.
000127743 536__ $$0G:(DE-HGF)POF3-311$$a311 - Signalling pathways, cell and tumor biology (POF3-311)$$cPOF3-311$$fPOF III$$x0
000127743 588__ $$aDataset connected to CrossRef, PubMed,
000127743 650_7 $$2NLM Chemicals$$aReactive Oxygen Species
000127743 7001_ $$0P:(DE-He78)f2177f299ad93efd161811e331914297$$aLier, Amelie$$b1$$udkfz
000127743 7001_ $$0P:(DE-HGF)0$$aGeiselhart, Anja$$b2
000127743 7001_ $$0P:(DE-HGF)0$$aThalheimer, Frederic B$$b3
000127743 7001_ $$0P:(DE-HGF)0$$aHuntscha, Sina$$b4
000127743 7001_ $$0P:(DE-HGF)0$$aSobotta, Mirko C$$b5
000127743 7001_ $$aMoehrle, Bettina$$b6
000127743 7001_ $$0P:(DE-He78)3860e24c3868c15255c3383a58e8d5b8$$aBrocks, David$$b7$$udkfz
000127743 7001_ $$0P:(DE-HGF)0$$aBayindir, Irem$$b8
000127743 7001_ $$0P:(DE-He78)6d878e5c991d4938a3ee892d27309a38$$aKaschutnig, Paul Emanuel$$b9$$udkfz
000127743 7001_ $$0P:(DE-HGF)0$$aMuedder, Katja$$b10
000127743 7001_ $$0P:(DE-He78)0812f68beb25392984d3abbe3c58b6d2$$aKlein, Corinna$$b11$$udkfz
000127743 7001_ $$aJauch, Anna$$b12
000127743 7001_ $$aSchroeder, Timm$$b13
000127743 7001_ $$aGeiger, Hartmut$$b14
000127743 7001_ $$0P:(DE-He78)7f55a0ed8b021080de00960cc73768fb$$aDick, Tobias$$b15$$udkfz
000127743 7001_ $$0P:(DE-He78)457c042884c901eb0a02c18bb1d30103$$aHolland-Letz, Tim$$b16$$udkfz
000127743 7001_ $$0P:(DE-He78)141ce740f5d881812d2675147b72ecaf$$aSchmezer, Peter$$b17$$udkfz
000127743 7001_ $$0P:(DE-HGF)0$$aLane, Steven W$$b18
000127743 7001_ $$aRieger, Michael A$$b19
000127743 7001_ $$0P:(DE-He78)ba3fae49054b6bfaaa289b05ecd936d6$$aEssers, Marieke$$b20$$udkfz
000127743 7001_ $$aWilliams, David A$$b21
000127743 7001_ $$0P:(DE-He78)732f4fbcddb0042251aa759a2e74d3b2$$aTrumpp, Andreas$$b22$$udkfz
000127743 7001_ $$0P:(DE-He78)7b613cadb8c16ce178713e15b85d982c$$aMilsom, Michael$$b23$$eLast author$$udkfz
000127743 773__ $$0PERI:(DE-600)1413423-8$$a10.1038/nature14131$$gVol. 520, no. 7548, p. 549 - 552$$n7548$$p549 - 552$$tNature <London>$$v520$$x1476-4687$$y2015
000127743 909CO $$ooai:inrepo02.dkfz.de:127743$$pVDB
000127743 9101_ $$0I:(DE-588b)2036810-0$$6P:(DE-HGF)0$$aDeutsches Krebsforschungszentrum$$b0$$kDKFZ
000127743 9101_ $$0I:(DE-588b)2036810-0$$6P:(DE-He78)f2177f299ad93efd161811e331914297$$aDeutsches Krebsforschungszentrum$$b1$$kDKFZ
000127743 9101_ $$0I:(DE-588b)2036810-0$$6P:(DE-HGF)0$$aDeutsches Krebsforschungszentrum$$b2$$kDKFZ
000127743 9101_ $$0I:(DE-HGF)0$$6P:(DE-HGF)0$$aExternal Institute$$b3$$kExtern
000127743 9101_ $$0I:(DE-588b)2036810-0$$6P:(DE-HGF)0$$aDeutsches Krebsforschungszentrum$$b4$$kDKFZ
000127743 9101_ $$0I:(DE-588b)2036810-0$$6P:(DE-HGF)0$$aDeutsches Krebsforschungszentrum$$b5$$kDKFZ
000127743 9101_ $$0I:(DE-588b)2036810-0$$6P:(DE-He78)3860e24c3868c15255c3383a58e8d5b8$$aDeutsches Krebsforschungszentrum$$b7$$kDKFZ
000127743 9101_ $$0I:(DE-588b)2036810-0$$6P:(DE-HGF)0$$aDeutsches Krebsforschungszentrum$$b8$$kDKFZ
000127743 9101_ $$0I:(DE-588b)2036810-0$$6P:(DE-He78)6d878e5c991d4938a3ee892d27309a38$$aDeutsches Krebsforschungszentrum$$b9$$kDKFZ
000127743 9101_ $$0I:(DE-588b)2036810-0$$6P:(DE-HGF)0$$aDeutsches Krebsforschungszentrum$$b10$$kDKFZ
000127743 9101_ $$0I:(DE-588b)2036810-0$$6P:(DE-He78)0812f68beb25392984d3abbe3c58b6d2$$aDeutsches Krebsforschungszentrum$$b11$$kDKFZ
000127743 9101_ $$0I:(DE-588b)2036810-0$$6P:(DE-He78)7f55a0ed8b021080de00960cc73768fb$$aDeutsches Krebsforschungszentrum$$b15$$kDKFZ
000127743 9101_ $$0I:(DE-588b)2036810-0$$6P:(DE-He78)457c042884c901eb0a02c18bb1d30103$$aDeutsches Krebsforschungszentrum$$b16$$kDKFZ
000127743 9101_ $$0I:(DE-588b)2036810-0$$6P:(DE-He78)141ce740f5d881812d2675147b72ecaf$$aDeutsches Krebsforschungszentrum$$b17$$kDKFZ
000127743 9101_ $$0I:(DE-588b)2036810-0$$6P:(DE-He78)ba3fae49054b6bfaaa289b05ecd936d6$$aDeutsches Krebsforschungszentrum$$b20$$kDKFZ
000127743 9101_ $$0I:(DE-588b)2036810-0$$6P:(DE-He78)732f4fbcddb0042251aa759a2e74d3b2$$aDeutsches Krebsforschungszentrum$$b22$$kDKFZ
000127743 9101_ $$0I:(DE-588b)2036810-0$$6P:(DE-He78)7b613cadb8c16ce178713e15b85d982c$$aDeutsches Krebsforschungszentrum$$b23$$kDKFZ
000127743 9131_ $$0G:(DE-HGF)POF3-311$$1G:(DE-HGF)POF3-310$$2G:(DE-HGF)POF3-300$$3G:(DE-HGF)POF3$$4G:(DE-HGF)POF$$aDE-HGF$$bGesundheit$$lKrebsforschung$$vSignalling pathways, cell and tumor biology$$x0
000127743 9141_ $$y2015
000127743 915__ $$0StatID:(DE-HGF)0420$$2StatID$$aNationallizenz
000127743 915__ $$0StatID:(DE-HGF)0200$$2StatID$$aDBCoverage$$bSCOPUS
000127743 915__ $$0StatID:(DE-HGF)0300$$2StatID$$aDBCoverage$$bMedline
000127743 915__ $$0StatID:(DE-HGF)0310$$2StatID$$aDBCoverage$$bNCBI Molecular Biology Database
000127743 915__ $$0StatID:(DE-HGF)0100$$2StatID$$aJCR$$bNATURE : 2015
000127743 915__ $$0StatID:(DE-HGF)0600$$2StatID$$aDBCoverage$$bEbsco Academic Search
000127743 915__ $$0StatID:(DE-HGF)0030$$2StatID$$aPeer Review$$bASC
000127743 915__ $$0StatID:(DE-HGF)0199$$2StatID$$aDBCoverage$$bThomson Reuters Master Journal List
000127743 915__ $$0StatID:(DE-HGF)0110$$2StatID$$aWoS$$bScience Citation Index
000127743 915__ $$0StatID:(DE-HGF)0150$$2StatID$$aDBCoverage$$bWeb of Science Core Collection
000127743 915__ $$0StatID:(DE-HGF)0111$$2StatID$$aWoS$$bScience Citation Index Expanded
000127743 915__ $$0StatID:(DE-HGF)1060$$2StatID$$aDBCoverage$$bCurrent Contents - Agriculture, Biology and Environmental Sciences
000127743 915__ $$0StatID:(DE-HGF)1030$$2StatID$$aDBCoverage$$bCurrent Contents - Life Sciences
000127743 915__ $$0StatID:(DE-HGF)1150$$2StatID$$aDBCoverage$$bCurrent Contents - Physical, Chemical and Earth Sciences
000127743 915__ $$0StatID:(DE-HGF)1040$$2StatID$$aDBCoverage$$bZoological Record
000127743 915__ $$0StatID:(DE-HGF)1050$$2StatID$$aDBCoverage$$bBIOSIS Previews
000127743 915__ $$0StatID:(DE-HGF)9930$$2StatID$$aIF >= 30$$bNATURE : 2015
000127743 9201_ $$0I:(DE-He78)A010-20160331$$kA010$$lStammzellen und Krebs$$x0
000127743 9201_ $$0I:(DE-He78)A160-20160331$$kA160$$lRedoxregulation$$x1
000127743 9201_ $$0I:(DE-He78)A012-20160331$$kA012$$lExperimentelle Hämatologie$$x2
000127743 9201_ $$0I:(DE-He78)A011-20160331$$kA011$$lStressinduzierte Aktivierung von hämatopoetischen Stammzellen$$x3
000127743 9201_ $$0I:(DE-He78)C060-20160331$$kC060$$lBiostatistik$$x4
000127743 9201_ $$0I:(DE-He78)C010-20160331$$kC010$$lEpigenomik und Krebsrisikofaktoren$$x5
000127743 980__ $$ajournal
000127743 980__ $$aVDB
000127743 980__ $$aI:(DE-He78)A010-20160331
000127743 980__ $$aI:(DE-He78)A160-20160331
000127743 980__ $$aI:(DE-He78)A012-20160331
000127743 980__ $$aI:(DE-He78)A011-20160331
000127743 980__ $$aI:(DE-He78)C060-20160331
000127743 980__ $$aI:(DE-He78)C010-20160331
000127743 980__ $$aUNRESTRICTED