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

Research output: Contribution to journalArticle

Authors

  • Florian Bonkhofer
  • Rossella Rispoli
  • Philip Pinheiro
  • Monika Krecsmarik
  • Janina Schneider-Swales
  • Ingrid Ho Ching Tsang
  • Marella de Bruijn
  • Tessa Peterkin
  • Roger Patient

Colleges, School and Institutes

External organisations

  • Molecular Haematology Unit, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, University of Oxford, Oxford, OX3 9DS, UK.
  • Division of Genetics and Molecular Medicine, NIHR Biomedical Research Centre, Guy's and St Thomas' NHS Foundation Trust and King's College London, London, UK.
  • BHF Centre of Research Excellence, Oxford, UK.
  • BHF Centre of Research Excellence, Oxford, UK. roger.patient@imm.ox.ac.uk.

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.

Details

Original languageEnglish
Article number3577
Number of pages14
JournalNature Communications
Volume10
Issue number1
Publication statusPublished - 8 Aug 2019