Loading...
Cis inhibition of NOTCH1 through JAGGED1 sustains embryonic hematopoietic stem cell fate
Thambyrajah, R. Maqueda, M. Neo, Wen H Imbach, K. Guillén, Y. Grases, D. Fadlullah, Z. Gambera, S. Matteini, F. Wang, X.
Thambyrajah, R.
Maqueda, M.
Neo, Wen H
Imbach, K.
Guillén, Y.
Grases, D.
Fadlullah, Z.
Gambera, S.
Matteini, F.
Wang, X.
Citations
Altmetric:
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.
Description
Date
2024
Publisher
Collections
Files
Keywords
Type
Article
Citation
Thambyrajah R, Maqueda M, Neo WH, Imbach K, Guillén Y, Grases D, et al. Cis inhibition of NOTCH1 through JAGGED1 sustains embryonic hematopoietic stem cell fate. Nature communications. 2024 Feb 21;15(1):1604. PubMed PMID: 38383534. Pubmed Central PMCID: PMC10882055. Epub 2024/02/22. eng.