Mimicry of embryonic circulation enhances the hoxa hemogenic niche and human blood development.
Cell Rep
; 40(11): 111339, 2022 09 13.
Article
en En
| MEDLINE
| ID: mdl-36103836
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-ß 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.
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Texto completo:
1
Base de datos:
MEDLINE
Asunto principal:
Hematopoyesis
/
Mesonefro
Idioma:
En
Revista:
Cell Rep
Año:
2022
Tipo del documento:
Article