Notch signal strength controls cell fate in the haemogenic endothelium.

Gama-Norton, Leonor; Ferrando Martorell, Eva, 1986-; Ruiz Herguido, Cristina; Liu, Zenhy; Guiu Sagarra, Jordi, 1983-; Islam, Abul, 1978-; Lee, Sung-Uk; Yan, Minhong; Guidos, Cynthia J.; López Bigas, Núria; Maeda, Takahiro; Espinosa Blay, Lluís; Kopan, Raphael; Bigas Salvans, Anna

Notch signal strength controls cell fate in the haemogenic endothelium.

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dc.contributor.author Gama-Norton, Leonorca
dc.contributor.author Ferrando Martorell, Eva, 1986-ca
dc.contributor.author Ruiz Herguido, Cristinaca
dc.contributor.author Liu, Zenhyca
dc.contributor.author Guiu Sagarra, Jordi, 1983-ca
dc.contributor.author Islam, Abul, 1978-ca
dc.contributor.author Lee, Sung-Ukca
dc.contributor.author Yan, Minhongca
dc.contributor.author Guidos, Cynthia J.ca
dc.contributor.author López Bigas, Núriaca
dc.contributor.author Maeda, Takahiroca
dc.contributor.author Espinosa Blay, Lluísca
dc.contributor.author Kopan, Raphaelca
dc.contributor.author Bigas Salvans, Annaca
dc.date.accessioned 2016-01-29T08:45:35Z
dc.date.available 2016-01-29T08:45:35Z
dc.date.issued 2015
dc.description.abstract Acquisition of the arterial and haemogenic endothelium fates concurrently occur in the aorta-gonad-mesonephros (AGM) region prior to haematopoietic stem cell (HSC) generation. The arterial programme depends on Dll4 and the haemogenic endothelium/HSC on Jag1-mediated Notch1 signalling. How Notch1 distinguishes and executes these different programmes in response to particular ligands is poorly understood. By using two Notch1 activation trap mouse models with different sensitivity, here we show that arterial endothelial cells and HSCs originate from distinct precursors, characterized by different Notch1 signal strengths. Microarray analysis on AGM subpopulations demonstrates that the Jag1 ligand stimulates low Notch strength, inhibits the endothelial programme and is permissive for HSC specification. In the absence of Jag1, endothelial cells experience high Dll4-induced Notch activity and select the endothelial programme, thus precluding HSC formation. Interference with the Dll4 signal by ligand-specific blocking antibodies is sufficient to inhibit the endothelial programme and favour specification of the haematopoietic lineage.ca
dc.description.sponsorship L.G.-N. was a recipient of Marie Curie Intra-European Fellowship (PIEF-GA-2011- 302226). E.F. and J.G. are recipients of FPI (BES-2011-048360 and BES-2008-005708, respectively). This research was funded by the Ministerio de Economıa y Competitividad (PLE2009-0111, SAF2010-15450, SAF2013-40922-R), Red Tematica de Investigacion Cooperativa en Cancer (RTICC) (RD12/0036/0054), Age`ncia de Gestio d’Ajuds Universitaris i de Recerca (AGAUR; 2014SGR-124) to A.B.
dc.format.mimetype application/pdfca
dc.identifier.citation Gama-Norton L, Ferrando E, Ruiz-Herguido C, Liu Z, Guiu J, Islam AB. et al. Notch signal strength controls cell fate in the haemogenic endothelium. Nat Commun. 2015 Oct 14;6:8510. DOI: 10.1038/ncomms9510.ca
dc.identifier.doi http://dx.doi.org/10.1038/ncomms9510
dc.identifier.issn 2041-1723
dc.identifier.uri http://hdl.handle.net/10230/25699
dc.language.iso engca
dc.publisher Nature Publishing Groupca
dc.relation.ispartof Nature Communications. 2015 Oct 14;6:8510
dc.relation.projectID info:eu-repo/grantAgreement/EC/FP7/302226
dc.relation.projectID info:eu-repo/grantAgreement/ES/3PN/BES2011-048360
dc.relation.projectID info:eu-repo/grantAgreement/ES/3PN/BES2008-005708
dc.relation.projectID info:eu-repo/grantAgreement/ES/3PN/PLE2009-0111
dc.relation.projectID info:eu-repo/grantAgreement/ES/3PN/SAF2010-15450
dc.relation.projectID info:eu-repo/grantAgreement/ES/1PE/SAF2013-40922
dc.rights This work is licensed under http://creativecommons.org/licenses/by/4.0/. The images or other third party material in this/narticle are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material.ca
dc.rights.accessRights info:eu-repo/semantics/openAccessca
dc.rights.uri http://creativecommons.org/licenses/by/4.0/ca
dc.subject.other Sistema hematopoèticca
dc.subject.other Cèl·lules mare hematopoètiquesca
dc.subject.other Artèries -- Fisiologiaca
dc.title Notch signal strength controls cell fate in the haemogenic endothelium.ca
dc.type info:eu-repo/semantics/articleca
dc.type.version info:eu-repo/semantics/publishedVersionca

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