2026-07-11T02:49:51Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/203202024-09-27T08:29:24Zcom_20.500.12105_19604com_20.500.12105_2051col_20.500.12105_19605
Repisalud
author
Thambyrajah, Roshana
author
Maqueda, Maria
author
Neo, Wen Hao
author
Imbach, Kathleen
author
Guillén, Yolanda
author
Grases, Daniela
author
Fadlullah, Zaki
author
Gambera, Stefano
author
Matteini, Francesca
author
Wang, Xiaonan
author
Calero-Nieto, Fernando J
author
Esteller, Manel
author
Florian, Maria Carolina
author
Porta, Eduard
author
Benedito, Rui
author
Göttgens, Berthold
author
Lacaud, Georges
author
Espinosa, Lluis
author
Bigas, Anna
funder
Agencia Estatal de Investigación (España)
funder
Cancer Research UK (Reino Unido)
funder
Ministerio de Ciencia e Innovación (España)
2024-07-09T10:13:19Z
2024-07-09T10:13:19Z
2024-02-21
Nat Commun. 2024 Feb 21;15(1):1604.
10.1038/s41467-024-45716-y
2041-1723
Nature communications
38383534
http://hdl.handle.net/20.500.12105/20320
Hematopoietic stem cells (HSCs) develop from the hemogenic endothelium (HE) in the aorta- gonads-and mesonephros (AGM) region and reside within Intra-aortic hematopoietic clusters (IAHC) along with hematopoietic progenitors (HPC). The signalling mechanisms that distinguish HSCs from HPCs are unknown. Notch signaling is essential for arterial specification, IAHC formation and HSC activity, but current studies on how Notch segregates these different fates are inconsistent. We now demonstrate that Notch activity is highest in a subset of, GFI1 + , HSC-primed HE cells, and is gradually lost with HSC maturation. We uncover that the HSC phenotype is maintained due to increasing levels of NOTCH1 and JAG1 interactions on the surface of the same cell (cis) that renders the NOTCH1 receptor from being activated. Forced activation of the NOTCH1 receptor in IAHC activates a hematopoietic differentiation program. Our results indicate that NOTCH1-JAG1 cis-inhibition preserves the HSC phenotype in the hematopoietic clusters of the embryonic aorta.
eng
Cis inhibition of NOTCH1 through JAGGED1 sustains embryonic hematopoietic stem cell fate.
journal article
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URL
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application/pdf
Cis inhibition of NOTCH1 through_Nat Commun_2024.pdf
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https://repisalud.isciii.es/bitstreams/b79776cc-70c0-4b27-9e9f-47e83f65f83d/download
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text/plain
Cis inhibition of NOTCH1 through_Nat Commun_2024.pdf.txt