STAT5-regulated microRNA-193b controls haematopoietic stem and progenitor cell expansion by modulating cytokine receptor signalling
dc.contributor.author
Haetscher, Nadine
dc.contributor.author
Feuermann, Yonatan
dc.contributor.author
Wingert, Susanne
dc.contributor.author
Rehage, Maike
dc.contributor.author
Thalheimer, Frederic B.
dc.contributor.author
Weiser, Christian
dc.contributor.author
Bohnenberger, Hanibal
dc.contributor.author
Jung, Klaus
dc.contributor.author
Schroeder, Timm
dc.contributor.author
Serve, Hubert
dc.contributor.author
Oellerich, Thomas
dc.contributor.author
Hennighausen, Lothar
dc.contributor.author
Rieger, Michael A.
dc.date.accessioned
2018-09-07T09:48:40Z
dc.date.available
2017-06-11T21:41:28Z
dc.date.available
2018-09-07T09:48:40Z
dc.date.issued
2015
dc.identifier.issn
2041-1723
dc.identifier.other
10.1038/ncomms9928
en_US
dc.identifier.uri
http://hdl.handle.net/20.500.11850/107962
dc.identifier.doi
10.3929/ethz-b-000107962
dc.description.abstract
Haematopoietic stem cells (HSCs) require the right composition of microRNAs (miR) for proper life-long balanced blood regeneration. Here we show a regulatory circuit that prevents excessive HSC self-renewal by upregulation of miR-193b upon self-renewal promoting thrombopoietin (TPO)-MPL-STAT5 signalling. In turn, miR-193b restricts cytokine signalling, by targeting the receptor tyrosine kinase c-KIT. We generated a miR-193b knockout mouse model to unravel the physiological function of miR-193b in haematopoiesis. MiR-193b−/− mice show a selective gradual enrichment of functional HSCs, which are fully competent in multilineage blood reconstitution upon transplantation. The absence of miR-193b causes an accelerated expansion of HSCs, without altering cell cycle or survival, but by decelerating differentiation. Conversely, ectopic miR-193b expression restricts long-term repopulating HSC expansion and blood reconstitution. MiR-193b-deficient haematopoietic stem and progenitor cells exhibit increased basal and cytokine-induced STAT5 and AKT signalling. This STAT5-induced microRNA provides a negative feedback for excessive signalling to restrict uncontrolled HSC expansion.
en_US
dc.format
application/pdf
en_US
dc.language.iso
en
en_US
dc.publisher
Nature
dc.rights.uri
http://creativecommons.org/licenses/by/4.0/
dc.title
STAT5-regulated microRNA-193b controls haematopoietic stem and progenitor cell expansion by modulating cytokine receptor signalling
en_US
dc.type
Journal Article
dc.rights.license
Creative Commons Attribution 4.0 International
dc.date.published
2015-11-25
ethz.journal.title
Nature Communications
ethz.journal.volume
6
en_US
ethz.journal.abbreviated
Nat Commun
ethz.pages.start
8928
en_US
ethz.size
11 p.
en_US
ethz.version.deposit
publishedVersion
en_US
ethz.identifier.wos
ethz.identifier.scopus
ethz.identifier.nebis
007044158
ethz.publication.place
London
ethz.publication.status
published
en_US
ethz.leitzahl
ETH Zürich::00002 - ETH Zürich::00012 - Lehre und Forschung::00007 - Departemente::02060 - Dep. Biosysteme / Dep. of Biosystems Science and Eng.::03992 - Schroeder, Timm / Schroeder, Timm
en_US
ethz.leitzahl.certified
ETH Zürich::00002 - ETH Zürich::00012 - Lehre und Forschung::00007 - Departemente::02060 - Dep. Biosysteme / Dep. of Biosystems Science and Eng.::03992 - Schroeder, Timm / Schroeder, Timm
ethz.date.deposited
2017-06-11T21:42:07Z
ethz.source
ECIT
ethz.identifier.importid
imp593653c59744493193
ethz.ecitpid
pub:168730
ethz.eth
yes
en_US
ethz.availability
Open access
en_US
ethz.rosetta.installDate
2017-07-14T13:04:18Z
ethz.rosetta.lastUpdated
2024-02-02T05:58:50Z
ethz.rosetta.versionExported
true
ethz.COinS
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