Elsevier

Experimental Hematology

Volume 103, November 2021, Pages 30-39.e2
Experimental Hematology

Brief Communication
VEGF, FGF2, and BMP4 regulate transitions of mesoderm to endothelium and blood cells in a human model of yolk sac hematopoiesis

https://doi.org/10.1016/j.exphem.2021.08.006Get rights and content
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open access

Highlights

  • Methylcellulose blast colony assay mimics yolk sac hematopoiesis.

  • FGF2 and VEGF are critical signals for the progression of mesoderm into endothelium.

  • BMP4 is required for subsequent generation of blood from hemogenic endothelium.

  • Blocking BMP4 signaling phenocopies aspects of RUNX1 gene deletion.

Exogenous growth factors play an important role in mediating hematopoietic differentiation of human pluripotent stem cells. We explored the role of different factors in early human blood cell production using blast colony formation in methylcellulose as a surrogate assay for yolk sac hematopoiesis. A reporter cell line that read out endothelial (SOX17+) and hematopoietic (RUNX1C+) progenitors facilitated the identification of basic fibroblast growth and vascular endothelial growth factor as critical signals for the progression of mesoderm into endothelium. Bone morphogenetic protein 4 was needed for the subsequent generation of blood from hemogenic endothelium, and this was antagonized by Activin A or high concentrations of the WNT agonist CHIR-99021. Manipulations of the Hedgehog pathway or inhibition of Notch signaling reduced blast colony frequency but did not perturb cell differentiation. These data help to define distinct roles for prerequisite growth factors that commit mesoderm to hemogenic endothelium and subsequently allocate cells to blood lineages.

Cited by (0)

FFB, ESN, and AGE designed and performed experiments and interpreted data. FFB, EGS, and AGE wrote the article, which all authors edited and approved.

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EGS and AGE contributed equally to this work.