VEGF, FGF2, and BMP4 regulate transitions of mesoderm to endothelium and blood cells in a human model of yolk sac hematopoiesis
| Autor: | Freya Bruveris, Elizabeth Ng, Edouard G. Stanley, Andrew G. Elefanty |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Vascular Endothelial Growth Factor A
Cancer Research Mesoderm Endothelium Cellular differentiation Bone Morphogenetic Protein 4 Biology Cell Line Genetics medicine Humans Yolk sac Induced pluripotent stem cell Molecular Biology Yolk Sac Hemogenic endothelium Wnt signaling pathway Cell Biology Hematology Hematopoiesis Cell biology medicine.anatomical_structure Bone morphogenetic protein 4 embryonic structures Fibroblast Growth Factor 2 |
| Zdroj: | Experimental Hematology. 103:30-39.e2 |
| ISSN: | 0301-472X |
| DOI: | 10.1016/j.exphem.2021.08.006 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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