Notch signal strength controls cell fate in the haemogenic endothelium

• DOI: 10.1038/ncomms9510
• Publication Date: 2015-10-14T12:36:49Z
• Authors: Leonor Gama-Norton; Eva Ferrando; Cristina Ruiz-Her...; Zhenyi Liu; Jordi Guiu; Abul B. M. M. K. ...; Sung-Uk Lee; Minhong Yan; Cynthia J. Guidos; Nuria López-Bigas; Takahiro Maeda; Lluis Espinosa; Raphael Kopan; Anna Bigas
• Keywords: JAG1

Abstract Acquisition of the arterial and haemogenic endothelium fates concurrently occur in aorta–gonad–mesonephros (AGM) region prior to haematopoietic stem cell (HSC) generation. The programme depends on Dll4 endothelium/HSC Jag1-mediated Notch1 signalling. How distinguishes executes these different programmes response particular ligands is poorly understood. By using two activation trap mouse models with sensitivity, here we show that endothelial cells HSCs originate from distinct precursors, characterized by signal strengths. Microarray analysis AGM subpopulations demonstrates Jag1 ligand stimulates low Notch strength, inhibits permissive for HSC specification. In absence Jag1, experience high Dll4-induced activity select programme, thus precluding formation. Interference ligand-specific blocking antibodies sufficient inhibit favour specification lineage.