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

Jingjing Li; Osmond Lao; Freya F Bruveris; Liyuan Wang; Kajal Chaudry; Ziqi Yang; Nona Farbehi; Elizabeth S Ng; Edouard G Stanley; Richard P Harvey; Andrew G Elefanty; Robert E Nordon

doi:10.1016/j.celrep.2022.111339

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

Cell Rep. 2022 Sep 13;40(11):111339. doi: 10.1016/j.celrep.2022.111339.

Authors

Affiliations

¹ Graduate School of Biomedical Engineering, University of New South Wales, Sydney, NSW, Australia.
² Murdoch Children's Research Institute, The Royal Children's Hospital, Flemington Road, Parkville, VIC 3052, Australia; Department of Paediatrics, Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne, Parkville, VIC 3052, Australia; The Novo Nordisk Foundation Center for Stem Cell Medicine (reNEW), Murdoch Children's Research Institute, Parkville, VIC 3052, Australia.
³ Graduate School of Biomedical Engineering, University of New South Wales, Sydney, NSW, Australia; Victor Chang Cardiac Research Institute. School of Clinical Medicine, University of New South Wales, Sydney, NSW, Australia; Garvan Weizmann Centre for Cellular Genomics, Garvan Institute of Medical Research, Sydney, NSW 2010, Australia.
⁴ Murdoch Children's Research Institute, The Royal Children's Hospital, Flemington Road, Parkville, VIC 3052, Australia; The Novo Nordisk Foundation Center for Stem Cell Medicine (reNEW), Murdoch Children's Research Institute, Parkville, VIC 3052, Australia.
⁵ Victor Chang Cardiac Research Institute. School of Clinical Medicine, University of New South Wales, Sydney, NSW, Australia.
⁶ Graduate School of Biomedical Engineering, University of New South Wales, Sydney, NSW, Australia. Electronic address: r.nordon@unsw.edu.au.

PMID: 36103836
DOI: 10.1016/j.celrep.2022.111339

Abstract

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.

Keywords: AGM hematopoiesis; CP: Stem cell research; fluid shear stress; human embryonic stem cell; lab on a chip; live cell imaging; single-cell RNA sequencing.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adult
Antigens, CD34
Cell Differentiation
Hematopoiesis*
Hematopoietic Stem Cells
Humans
Mesonephros*
Yolk Sac

Substances

Antigens, CD34

Associated data

figshare/10.6084/m9.figshare.14722392.v1