Work

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

Year: 2022

Type: article

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.

Source: Cell Reports

DOI: 10.1016/j.celrep.2022.111339

Authors: 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

Institutions: UNSW Sydney, Royal Children's Hospital, The University of Melbourne, Murdoch Children's Research Institute, Novo Nordisk Foundation Center for Stem Cell Medicine, Garvan Institute of Medical Research, Victor Chang Cardiac Research Institute

Language: English

Topic: Hematopoietic Stem Cell Transplantation

Subfield: Hematology

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $5,200

Funders: Stem Cells Australia, University of New South Wales, State Government of Victoria, Novo Nordisk Fonden, Australian Research Council, National Health and Medical Research Council

Awards: Molecular mechanisms and therapeutic approaches to cardiac development, regeneration and disease, Transcriptional regulation of definitive hematopoietic development in humans, G4049518193, Recreating haematopoietic niches to support HSC generation from human pluripotent stem cells and to model bone marrow failure, Molecular Approaches to Cardiac Development, Disease and Regeneration, Characterization of HOXA-expressing human haematopoietic cells generated from embryonic stem cells, Haematopoietic stem cells from human pluripotent stem cells: the future of bone marrow transplantation, Pluripotent stem cells & medical research

OpenAlex ID: W4295898294

FWCI: 1.792

Cites: 80

Cited by: 12

Related to: 10