Mimicry of embryonic circulation enhances the hoxa hemogenic niche and human blood development

Li, Jingjing and Lao, Osmond and Bruveris, Freya F. and Wang, Liyuan and Chaudry, Kajal and Yang, Ziqi and Farbehi, Nona and Ng, Elizabeth S. and Stanley, Edouard G. and Harvey, Richard P. and Elefanty, Andrew G. and Nordon, Robert E. (2022) Mimicry of embryonic circulation enhances the hoxa hemogenic niche and human blood development. Cell Reports, 40 (11). p. 111339. ISSN 22111247

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Link to published document: http://doi.org/10.1016/j.celrep.2022.111339


Precursors of the adult hematopoietic system arise from the aorta-gonad-mesonephros (AGM) region shortly after the embryonic circulation is established. Here, we develop a microfluidic culture system to mimic the primitive embryonic circulation and address the hypothesis that circulatory flow and shear stress enhance embryonic blood development. Embryonic (HOXA+) hematopoiesis was derived from human pluripotent stem cells and induced from mesoderm by small-molecule manipulation of TGF-β and WNT signaling (SB/CHIR). Microfluidic and orbital culture promoted the formation of proliferative CD34+RUNX1C-GFP+SOX17-mCHERRY+ precursor cells that were released into the artificial circulation from SOX17+ arterial-like structures. Single-cell transcriptomic analysis delineated extra-embryonic (yolk sac) and HOXA+ embryonic blood differentiation pathways. SB/CHIR and circulatory flow enhance hematopoiesis by the formation of proliferative HOXA+RUNX1C+CD34+ precursor cells that differentiate into monocyte/macrophage, granulocyte, erythrocyte, and megakaryocyte progenitors. © 2022

Item Type: Article
Subjects: R Medicine > R Medicine (General)
Depositing User: Repository Administrator
Date Deposited: 02 Mar 2023 01:39
Last Modified: 02 Mar 2023 01:39
URI: http://eprints.victorchang.edu.au/id/eprint/1311

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