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The autophagy protein Atg7 is essential for hematopoietic stem cell maintenance.

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cam.issuedOnline2011-02-21
dc.contributor.authorMortensen, Monika
dc.contributor.authorSoilleux, Elizabeth J
dc.contributor.authorDjordjevic, Gordana
dc.contributor.authorTripp, Rebecca
dc.contributor.authorLutteropp, Michael
dc.contributor.authorSadighi-Akha, Elham
dc.contributor.authorStranks, Amanda J
dc.contributor.authorGlanville, Julie
dc.contributor.authorKnight, Samantha
dc.contributor.authorJacobsen, Sten-Eirik W
dc.contributor.authorKranc, Kamil R
dc.contributor.authorSimon, Anna Katharina
dc.contributor.orcidSoilleux, Elizabeth [0000-0002-4032-7249]
dc.date.accessioned2018-12-22T00:31:33Z
dc.date.available2018-12-22T00:31:33Z
dc.date.issued2011-03-14
dc.description.abstractThe role of autophagy, a lysosomal degradation pathway which prevents cellular damage, in the maintenance of adult mouse hematopoietic stem cells (HSCs) remains unknown. Although normal HSCs sustain life-long hematopoiesis, malignant transformation of HSCs leads to leukemia. Therefore, mechanisms protecting HSCs from cellular damage are essential to prevent hematopoietic malignancies. In this study, we crippled autophagy in HSCs by conditionally deleting the essential autophagy gene Atg7 in the hematopoietic system. This resulted in the loss of normal HSC functions, a severe myeloproliferation, and death of the mice within weeks. The hematopoietic stem and progenitor cell compartment displayed an accumulation of mitochondria and reactive oxygen species, as well as increased proliferation and DNA damage. HSCs within the Lin(-)Sca-1(+)c-Kit(+) (LSK) compartment were significantly reduced. Although the overall LSK compartment was expanded, Atg7-deficient LSK cells failed to reconstitute the hematopoietic system of lethally irradiated mice. Consistent with loss of HSC functions, the production of both lymphoid and myeloid progenitors was impaired in the absence of Atg7. Collectively, these data show that Atg7 is an essential regulator of adult HSC maintenance.
dc.format.mediumPrint-Electronic
dc.identifier.doi10.17863/CAM.34711
dc.identifier.eissn1540-9538
dc.identifier.issn0022-1007
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/287407
dc.languageeng
dc.language.isoeng
dc.publisherRockefeller University Press
dc.publisher.urlhttp://dx.doi.org/10.1084/jem.20101145
dc.rightsAttribution-NonCommercial-ShareAlike 4.0 International
dc.rights.urihttps://creativecommons.org/licenses/by-nc-sa/4.0/
dc.subjectAnimals
dc.subjectApoptosis
dc.subjectAutophagy
dc.subjectAutophagy-Related Protein 7
dc.subjectCell Proliferation
dc.subjectDNA Damage
dc.subjectFemale
dc.subjectHematopoietic Stem Cells
dc.subjectMale
dc.subjectMice
dc.subjectMice, Knockout
dc.subjectMicrotubule-Associated Proteins
dc.subjectMitochondria
dc.subjectMyeloproliferative Disorders
dc.subjectReactive Oxygen Species
dc.subjectStem Cells
dc.titleThe autophagy protein Atg7 is essential for hematopoietic stem cell maintenance.
dc.typeArticle
prism.endingPage467
prism.issueIdentifier3
prism.publicationDate2011
prism.publicationNameJ Exp Med
prism.startingPage455
prism.volume208
rioxxterms.licenseref.startdate2011-03
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserved
rioxxterms.typeJournal Article/Review
rioxxterms.versionVoR
rioxxterms.versionofrecord10.1084/jem.20101145

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