Cis inhibition of NOTCH1 through JAGGED1 sustains embryonic hematopoietic stem cell fate

Roshana Thambyrajah (), Maria Maqueda, Wen Hao Neo, Kathleen Imbach, Yolanda Guillén, Daniela Grases, Zaki Fadlullah, Stefano Gambera, Francesca Matteini, Xiaonan Wang, Fernando J. Calero-Nieto, Manel Esteller, Maria Carolina Florian, Eduard Porta, Rui Benedito, Berthold Göttgens, Georges Lacaud, Lluis Espinosa and Anna Bigas ()
Additional contact information
Roshana Thambyrajah: Program in Cancer Research. Institut Hospital del Mar d’Investigacions Mèdiques, CIBERONC
Maria Maqueda: Program in Cancer Research. Institut Hospital del Mar d’Investigacions Mèdiques, CIBERONC
Wen Hao Neo: The University of Manchester
Kathleen Imbach: Josep Carreras Leukemia Research Institute
Yolanda Guillén: Program in Cancer Research. Institut Hospital del Mar d’Investigacions Mèdiques, CIBERONC
Daniela Grases: Josep Carreras Leukemia Research Institute
Zaki Fadlullah: The University of Manchester
Stefano Gambera: Molecular Genetics of Angiogenesis Group. Centro Nacional de Investigaciones Cardiovasculares (CNIC)
Francesca Matteini: Stem Cell Aging Group, Regenerative Medicine Program, The Bellvitge Institute for Biomedical Research (IDIBELL)
Xiaonan Wang: Wellcome - MRC Cambridge Stem Cell Institute, Cambridge Biomedical Campus
Fernando J. Calero-Nieto: Wellcome - MRC Cambridge Stem Cell Institute, Cambridge Biomedical Campus
Manel Esteller: Josep Carreras Leukemia Research Institute
Maria Carolina Florian: Centro de Investigacion Biomedica en Red (CIBER)
Eduard Porta: Josep Carreras Leukemia Research Institute
Rui Benedito: Molecular Genetics of Angiogenesis Group. Centro Nacional de Investigaciones Cardiovasculares (CNIC)
Berthold Göttgens: Wellcome - MRC Cambridge Stem Cell Institute, Cambridge Biomedical Campus
Georges Lacaud: The University of Manchester
Lluis Espinosa: Program in Cancer Research. Institut Hospital del Mar d’Investigacions Mèdiques, CIBERONC
Anna Bigas: Program in Cancer Research. Institut Hospital del Mar d’Investigacions Mèdiques, CIBERONC

Nature Communications, 2024, vol. 15, issue 1, 1-18

Abstract: Abstract 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.

Date: 2024
References: Add references at CitEc
Citations: View citations in EconPapers (1)

Downloads: (external link)
https://www.nature.com/articles/s41467-024-45716-y 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:15:y:2024:i:1:d:10.1038_s41467-024-45716-y

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

DOI: 10.1038/s41467-024-45716-y

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 ().