PUBLICATION
Blood stem cell-forming haemogenic endothelium in zebrafish derives from arterial endothelium
- Authors
- Bonkhofer, F., Rispoli, R., Pinheiro, P., Krecsmarik, M., Schneider-Swales, J., Tsang, I.H.C., de Bruijn, M., Monteiro, R., Peterkin, T., Patient, R.
- ID
- ZDB-PUB-190810-3
- Date
- 2019
- Source
- Nature communications 10: 3577 (Journal)
- Registered Authors
- Monteiro, Rui, Patient, Roger K., Peterkin, Tessa, Pinheiro, Philip
- Keywords
- none
- Datasets
- GEO:GSE132258, GEO:GSE132260, GEO:GSE132259
- MeSH Terms
-
- Zebrafish/embryology*
- Zebrafish/metabolism
- Hemangioblasts/physiology*
- Arteries/cytology
- Arteries/embryology*
- Arteries/metabolism
- Core Binding Factor Alpha 2 Subunit/genetics
- Gene Knockout Techniques
- Animals, Genetically Modified
- Cell Lineage
- Embryonic Development
- Animals
- Zebrafish Proteins/genetics
- Zebrafish Proteins/metabolism
- Embryo, Nonmammalian
- Intracellular Signaling Peptides and Proteins/metabolism
- Endothelium, Vascular/cytology
- Endothelium, Vascular/embryology*
- Endothelium, Vascular/metabolism
- PubMed
- 31395869 Full text @ Nat. Commun.
Citation
Bonkhofer, F., Rispoli, R., Pinheiro, P., Krecsmarik, M., Schneider-Swales, J., Tsang, I.H.C., de Bruijn, M., Monteiro, R., Peterkin, T., Patient, R. (2019) Blood stem cell-forming haemogenic endothelium in zebrafish derives from arterial endothelium. Nature communications. 10:3577.
Abstract
Haematopoietic stem cells are generated from the haemogenic endothelium (HE) located in the floor of the dorsal aorta (DA). Despite being integral to arteries, it is controversial whether HE and arterial endothelium share a common lineage. Here, we present a transgenic zebrafish runx1 reporter line to isolate HE and aortic roof endothelium (ARE)s, excluding non-aortic endothelium. Transcriptomic analysis of these populations identifies Runx1-regulated genes and shows that HE initially expresses arterial markers at similar levels to ARE. Furthermore, runx1 expression depends on prior arterial programming by the Notch ligand dll4. Runx1-/- mutants fail to downregulate arterial genes in the HE, which remains integrated within the DA, suggesting that Runx1 represses the pre-existing arterial programme in HE to allow progression towards the haematopoietic fate. These findings strongly suggest that, in zebrafish, aortic endothelium is a precursor to HE, with potential implications for pluripotent stem cell differentiation protocols for the generation of transplantable HSCs.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping