Human yolk sac-like haematopoiesis generates RUNX1- and GFI1/1B-dependent blood and SOX17-positive endothelium

• DOI: 10.1242/dev.193037
• Publication Date: 2020-10-07T15:41:47Z
• Authors: Freya F. Bruveris; Elizabeth S. Ng; Ana Rita Leitoguinho; Ali Motazedian; Katerina Vlahos; Koula Sourris; Robyn Mayberry; Penelope McDonald; Lisa Azzola; Nadia M. Davidson; Alicia Oshlack; Edouard G. Stanley; Andrew G. Elefanty
• Keywords: RUNX1

The genetic regulatory network controlling early fate choices during human blood cell development are not well understood. We used pluripotent stem reporter lines to track the of endothelial and haematopoietic populations in an vitro model yolk-sac development. identified SOX17−CD34+CD43− cells at day 2 blast colony development, as a haemangioblast-like branch point from which SOX17−CD34+CD43+ SOX17+CD34+CD43− endothelium subsequently arose. Most was dependent on RUNX1. Deletion RUNX1 only permitted single wave yolk sac-like primitive erythropoiesis, but no sac myelopoiesis or aorta-gonad-mesonephros (AGM)-like haematopoiesis. Blocking GFI1/1B activity with small molecule inhibitor abrogated all even intact gene. Together, our data defines hierarchical requirements for both haematopoiesis arising SOX17-negative haemogenic intermediate.