Blood stem cell-forming haemogenic endothelium in zebrafish derives from arterial endothelium

Florian Bonkhofer, Rossella Rispoli, Philip Pinheiro, Monika Krecsmarik, Janina Schneider-Swales, Ingrid Ho Ching Tsang, Marella de Bruijn, Rui Monteiro (), Tessa Peterkin and Roger Patient ()
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Florian Bonkhofer: University of Oxford
Rossella Rispoli: University of Oxford
Philip Pinheiro: University of Oxford
Monika Krecsmarik: University of Oxford
Janina Schneider-Swales: University of Oxford
Ingrid Ho Ching Tsang: University of Oxford
Marella de Bruijn: University of Oxford
Rui Monteiro: University of Oxford
Tessa Peterkin: University of Oxford
Roger Patient: University of Oxford

Nature Communications, 2019, vol. 10, issue 1, 1-14

Abstract: 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.

Date: 2019
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DOI: 10.1038/s41467-019-11423-2

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