Gama-Norton, LeonorFerrando Martorell, Eva, 1986-Ruiz Herguido, CristinaLiu, ZenhyGuiu Sagarra, Jordi, 1983-Islam, Abul, 1978-Lee, Sung-UkYan, MinhongGuidos, Cynthia J.López Bigas, NúriaMaeda, TakahiroEspinosa Blay, LluísKopan, RaphaelBigas Salvans, Anna2016-01-292016-01-292015Gama-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/ncomms9510.2041-1723http://hdl.handle.net/10230/25699Acquisition 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.application/pdfengThis 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.Sistema hematopoèticCèl·lules mare hematopoètiquesArtèries -- Fisiologiainfo:eu-repo/semantics/articlehttp://dx.doi.org/10.1038/ncomms9510info:eu-repo/semantics/openAccess