Notch signal strength controls cell fate in the haemogenic endothelium

Leonor Gama-Norton, Eva Ferrando, Cristina Ruiz-Herguido, Zhenyi Liu, Jordi Guiu, Abul B. M. M. K. Islam, Sung-Uk Lee, Minhong Yan, Cynthia J. Guidos, Nuria López-Bigas, Takahiro Maeda, Lluis Espinosa, Raphael Kopan () and Anna Bigas ()
Additional contact information
Leonor Gama-Norton: Program in Cancer Research, Institut Hospital del Mar d’Investigacions Mèdiques (IMIM)
Eva Ferrando: Program in Cancer Research, Institut Hospital del Mar d’Investigacions Mèdiques (IMIM)
Cristina Ruiz-Herguido: Program in Cancer Research, Institut Hospital del Mar d’Investigacions Mèdiques (IMIM)
Zhenyi Liu: University of Cincinnati
Jordi Guiu: Program in Cancer Research, Institut Hospital del Mar d’Investigacions Mèdiques (IMIM)
Abul B. M. M. K. Islam: Research Unit on Biomedical Informatics, Universitat Pompeu Fabra
Sung-Uk Lee: Harvard Medical School, Brigham and Women's Hospital
Minhong Yan: Genentech
Cynthia J. Guidos: Program in Developmental and Stem Cell Biology, Hospital for Sick Children Research Institute
Nuria López-Bigas: Research Unit on Biomedical Informatics, Universitat Pompeu Fabra
Takahiro Maeda: Harvard Medical School, Brigham and Women's Hospital
Lluis Espinosa: Program in Cancer Research, Institut Hospital del Mar d’Investigacions Mèdiques (IMIM)
Raphael Kopan: University of Cincinnati
Anna Bigas: Program in Cancer Research, Institut Hospital del Mar d’Investigacions Mèdiques (IMIM)

Nature Communications, 2015, vol. 6, issue 1, 1-12

Abstract: 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.

Date: 2015
References: Add references at CitEc
Citations: View citations in EconPapers (1)

Downloads: (external link)
https://www.nature.com/articles/ncomms9510 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms9510

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/ncomms9510

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().