Blood stem cell-forming haemogenic endothelium in zebrafish derives from arterial endothelium
| Autor: | Bonkhofer, F, Rispoli, R, Pinheiro, P, Krecsmarik, M, Schneider-Swales, J, Tsang, I, De Bruijn, M, Monteiro, R, Peterkin, T, Patient, R |
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| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
Cell lineage
Embryo Nonmammalian Hemangioblasts Science Haematopoietic stem cells Intracellular Signaling Peptides and Proteins Embryonic Development Arteries Zebrafish Proteins Article Animals Genetically Modified Gene Knockout Techniques Haematopoiesis hemic and lymphatic diseases embryonic structures Core Binding Factor Alpha 2 Subunit cardiovascular system Animals lcsh:Q Endothelium Vascular lcsh:Science Zebrafish |
| Zdroj: | Nature Communications Nature Communications, Vol 10, Iss 1, Pp 1-14 (2019) |
| DOI: | 10.1038/s41467-019-11423-2 |
| Popis: | 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. HSCs emerge from haemogenic endothelium (HE) in the dorsal aorta but whether these tissues share a common lineage is unclear. Here, the authors use a zebrafish runx1 reporter to show that HE maintains an arterial gene expression profile in the absence of Runx1, suggesting the aortic endothelium as a precursor of HE. |
| Databáze: | OpenAIRE |
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