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dc.contributor.authorRenders, Simon
dc.contributor.authorSvendsen, Arthur Flohr
dc.contributor.authorPanten, Jasper
dc.contributor.authorRama, Nicolas
dc.contributor.authorMaryanovich, Maria
dc.contributor.authorSommerkamp, Pia
dc.contributor.authorLadel, Luisa
dc.contributor.authorRedavid, Anna Rita
dc.contributor.authorGibert, Benjamin
dc.contributor.authorLazare, Seka
dc.contributor.authorDucarouge, Benjamin
dc.contributor.authorSchönberger, Katharina
dc.contributor.authorNarr, Andreas
dc.contributor.authorTourbez, Manon
dc.contributor.authorDethmers-Ausema, Bertien
dc.contributor.authorZwart, Erik
dc.contributor.authorHotz-Wagenblatt, Agnes
dc.contributor.authorZhang, Dachuan
dc.contributor.authorKorn, Claudia
dc.contributor.authorZeisberger, Petra
dc.contributor.authorPrzybylla, Adriana
dc.contributor.authorSohn, Markus
dc.contributor.authorMendez-Ferrer, Simon
dc.contributor.authorHeikenwälder, Mathias
dc.contributor.authorBrune, Maik
dc.contributor.authorKlimmeck, Daniel
dc.contributor.authorBystrykh, Leonid
dc.contributor.authorFrenette, Paul S.
dc.contributor.authorMehlen, Patrick
dc.contributor.authorde Haan, Gerald
dc.contributor.authorCabezas-Wallscheid, Nina
dc.contributor.authorTrumpp, Andreas
dc.date.accessioned2021-01-27T16:15:25Z
dc.date.available2021-01-27T16:15:25Z
dc.date.issued2021-01-27
dc.date.submitted2019-09-07
dc.identifier.others41467-020-20801-0
dc.identifier.other20801
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/316773
dc.descriptionFunder: Studienstiftung des Deutschen Volkes (German National Academic Foundation); doi: https://doi.org/10.13039/501100004350
dc.descriptionFunder: Heinrich F.C. Behr Stiftung
dc.descriptionFunder: Dietmar Hopp Stiftung; doi: https://doi.org/10.13039/501100005941
dc.description.abstractAbstract: Haematopoietic stem cells (HSCs) are characterized by their self-renewal potential associated to dormancy. Here we identify the cell surface receptor neogenin-1 as specifically expressed in dormant HSCs. Loss of neogenin-1 initially leads to increased HSC expansion but subsequently to loss of self-renewal and premature exhaustion in vivo. Its ligand netrin-1 induces Egr1 expression and maintains quiescence and function of cultured HSCs in a Neo1 dependent manner. Produced by arteriolar endothelial and periarteriolar stromal cells, conditional netrin-1 deletion in the bone marrow niche reduces HSC numbers, quiescence and self-renewal, while overexpression increases quiescence in vivo. Ageing associated bone marrow remodelling leads to the decline of netrin-1 expression in niches and a compensatory but reversible upregulation of neogenin-1 on HSCs. Our study suggests that niche produced netrin-1 preserves HSC quiescence and self-renewal via neogenin-1 function. Decline of netrin-1 production during ageing leads to the gradual decrease of Neo1 mediated HSC self-renewal.
dc.languageen
dc.publisherNature Publishing Group UK
dc.rightsAttribution 4.0 International (CC BY 4.0)en
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/en
dc.subjectArticle
dc.subject/631/443/7
dc.subject/631/532/1542
dc.subject/631/532/2441
dc.subject/631/532/2139
dc.subject/13/31
dc.subject/38/91
dc.subject/13/51
dc.subject/13/100
dc.subject/13/106
dc.subject/14/19
dc.subject/64/60
dc.subjectarticle
dc.titleNiche derived netrin-1 regulates hematopoietic stem cell dormancy via its receptor neogenin-1
dc.typeArticle
dc.date.updated2021-01-27T16:15:24Z
prism.issueIdentifier1
prism.publicationNameNature Communications
prism.volume12
dc.identifier.doi10.17863/CAM.63887
dcterms.dateAccepted2020-12-14
rioxxterms.versionofrecord10.1038/s41467-020-20801-0
rioxxterms.versionVoR
rioxxterms.licenseref.urihttp://creativecommons.org/licenses/by/4.0/
dc.contributor.orcidRama, Nicolas [0000-0003-1614-7755]
dc.contributor.orcidMaryanovich, Maria [0000-0002-2015-0538]
dc.contributor.orcidGibert, Benjamin [0000-0002-5295-3124]
dc.contributor.orcidZwart, Erik [0000-0002-4552-003X]
dc.contributor.orcidZhang, Dachuan [0000-0002-1746-275X]
dc.contributor.orcidMendez-Ferrer, Simon [0000-0002-9805-9988]
dc.contributor.orcidHeikenwälder, Mathias [0000-0002-3135-2274]
dc.contributor.orcidBystrykh, Leonid [0000-0001-6924-5602]
dc.contributor.orcidFrenette, Paul S. [0000-0003-0862-9922]
dc.contributor.orcidde Haan, Gerald [0000-0001-9706-0138]
dc.contributor.orcidCabezas-Wallscheid, Nina [0000-0003-0870-0530]
dc.contributor.orcidTrumpp, Andreas [0000-0002-6212-3466]
dc.identifier.eissn2041-1723
pubs.funder-project-idEC | EU Framework Programme for Research and Innovation H2020 | H2020 Priority Excellent Science | H2020 European Research Council (H2020 Excellent Science - European Research Council) (ERC-Stg-2017)
pubs.funder-project-idDeutsche Forschungsgemeinschaft (German Research Foundation) (FOR2033, SFB873)


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Attribution 4.0 International (CC BY 4.0)
Except where otherwise noted, this item's licence is described as Attribution 4.0 International (CC BY 4.0)