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    Human yolk sac-like haematopoiesis generates RUNX1-, GFI1- and/or GFI1B-dependent blood and SOX17-positive endothelium

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    Author
    Bruveris, FF; Ng, ES; Leitoguinho, AR; Motazedian, A; Vlahos, K; Sourris, K; Mayberry, R; McDonald, P; Azzola, L; Davidson, NM; ...
    Date
    2020-10-01
    Source Title
    Development (Cambridge)
    Publisher
    COMPANY BIOLOGISTS LTD
    University of Melbourne Author/s
    Davidson, Nadia; Oshlack, Alicia; Elefanty, Andrew; Stanley, Edouard; Bruveris, Freya; Leitoguinho, Ana Rita; Motazedian, Ali
    Affiliation
    School of BioSciences
    School of Physics
    Paediatrics (RCH)
    Metadata
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    Document Type
    Journal Article
    Citations
    Bruveris, F. F., Ng, E. S., Leitoguinho, A. R., Motazedian, A., Vlahos, K., Sourris, K., Mayberry, R., McDonald, P., Azzola, L., Davidson, N. M., Oshlack, A., Stanley, E. G. & Elefanty, A. G. (2020). Human yolk sac-like haematopoiesis generates RUNX1-, GFI1- and/or GFI1B-dependent blood and SOX17-positive endothelium. DEVELOPMENT, 147 (20), https://doi.org/10.1242/dev.193037.
    Access Status
    Open Access
    URI
    http://hdl.handle.net/11343/252215
    DOI
    10.1242/dev.193037
    Open Access at PMC
    http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7648599
    Abstract
    The genetic regulatory network controlling early fate choices during human blood cell development are not well understood. We used human pluripotent stem cell reporter lines to track the development of endothelial and haematopoietic populations in an in vitro model of human yolk-sac development. We identified SOX17-CD34+CD43- endothelial cells at day 2 of blast colony development, as a haemangioblast-like branch point from which SOX17-CD34+CD43+ blood cells and SOX17+CD34+CD43- endothelium subsequently arose. Most human blood cell development was dependent on RUNX1. Deletion of RUNX1 only permitted a single wave of yolk sac-like primitive erythropoiesis, but no yolk sac myelopoiesis or aorta-gonad-mesonephros (AGM)-like haematopoiesis. Blocking GFI1 and/or GFI1B activity with a small molecule inhibitor abrogated all blood cell development, even in cell lines with an intact RUNX1 gene. Together, our data define the hierarchical requirements for RUNX1, GFI1 and/or GFI1B during early human haematopoiesis arising from a yolk sac-like SOX17-negative haemogenic endothelial intermediate.

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