Notch signal strength controls cell fate in the haemogenic endothelium

Leonor Gama-Norton, Eva Ferrando, Cristina Ruiz-Herguido, Zenhy 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, Anna Bigas

研究成果: ジャーナルへの寄稿記事

46 引用 (Scopus)

抄録

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.

元の言語英語
記事番号8510
ジャーナルNature communications
6
DOI
出版物ステータス出版済み - 10 14 2015

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endothelium
notches
Hematopoietic Stem Cells
Stem cells
stem cells
Endothelium
Mesonephros
gonads
Endothelial cells
Gonads
Ligands
aorta
cells
Aorta
notch strength
Endothelial Cells
ligands
specifications
Specifications
Blocking Antibodies

All Science Journal Classification (ASJC) codes

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

これを引用

Gama-Norton, L., Ferrando, E., Ruiz-Herguido, C., Liu, Z., Guiu, J., Islam, A. B. M. M. K., ... Bigas, A. (2015). Notch signal strength controls cell fate in the haemogenic endothelium. Nature communications, 6, [8510]. https://doi.org/10.1038/ncomms9510

Notch signal strength controls cell fate in the haemogenic endothelium. / Gama-Norton, Leonor; Ferrando, Eva; Ruiz-Herguido, Cristina; Liu, Zenhy; Guiu, Jordi; Islam, Abul B.M.M.K.; Lee, Sung Uk; Yan, Minhong; Guidos, Cynthia J.; López-Bigas, Nuria; Maeda, Takahiro; Espinosa, Lluis; Kopan, Raphael; Bigas, Anna.

:: Nature communications, 巻 6, 8510, 14.10.2015.

研究成果: ジャーナルへの寄稿記事

Gama-Norton, L, Ferrando, E, Ruiz-Herguido, C, Liu, Z, Guiu, J, Islam, ABMMK, Lee, SU, Yan, M, Guidos, CJ, López-Bigas, N, Maeda, T, Espinosa, L, Kopan, R & Bigas, A 2015, 'Notch signal strength controls cell fate in the haemogenic endothelium', Nature communications, 巻. 6, 8510. https://doi.org/10.1038/ncomms9510
Gama-Norton L, Ferrando E, Ruiz-Herguido C, Liu Z, Guiu J, Islam ABMMK その他. Notch signal strength controls cell fate in the haemogenic endothelium. Nature communications. 2015 10 14;6. 8510. https://doi.org/10.1038/ncomms9510
Gama-Norton, Leonor ; Ferrando, Eva ; Ruiz-Herguido, Cristina ; Liu, Zenhy ; Guiu, Jordi ; Islam, Abul B.M.M.K. ; Lee, Sung Uk ; Yan, Minhong ; Guidos, Cynthia J. ; López-Bigas, Nuria ; Maeda, Takahiro ; Espinosa, Lluis ; Kopan, Raphael ; Bigas, Anna. / Notch signal strength controls cell fate in the haemogenic endothelium. :: Nature communications. 2015 ; 巻 6.
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