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VEGF-A165 augments erythropoietic development from human embryonic stem cells
Chantal Cerdan1, Anne Rouleau, Mickie Bhatia
1Robarts Research Institute, Stem Cell Biology and Regenerative Medicine, The University of Western Ontario, London, ON, Canada.
Blood
|December 6, 2003
Summary
Vascular Endothelial Growth Factor (VEGF-A165) promotes red blood cell development from human embryonic stem cells (hESCs). This finding offers the first evidence of a factor regulating hematopoietic lineage commitment in hESCs.
Area of Science:
- Stem cell biology
- Hematopoiesis research
- Developmental biology
Background:
- Hematopoietic cell fate in human embryonic stem cells (hESCs) can be augmented by cytokines and BMP-4.
- Factors regulating specific hematopoietic lineage commitment from hESCs remain largely unreported.
Purpose of the Study:
- To investigate the role of vascular endothelial growth factor (VEGF-A165) in directing hematopoietic lineage commitment from hESCs.
- To identify factors capable of regulating erythropoiesis in hESC-derived hematopoiesis.
Main Methods:
- Human embryonic stem cells (hESCs) were differentiated into embryoid bodies (EBs) in the presence of hematopoietic cytokines, BMP-4, and VEGF-A165.
- Flow cytometry and gene expression analysis were used to assess hematopoietic and erythroid marker expression.
- The effects on globin chain synthesis and self-renewal potential were evaluated.
Main Results:
- VEGF-A165 selectively promoted erythropoietic development from hESCs, dependent on cytokines and BMP-4.
- VEGF-A165 increased CD34+KDR+ cells and erythroid marker expression, including embryonic globins (zeta and epsilon).
- VEGF-A165 enhanced the self-renewal of primitive hematopoietic cells with erythroid progenitor capacity.
Conclusions:
- VEGF-A165 plays a significant role in promoting erythropoiesis during hESC differentiation.
- This study provides the first evidence for a factor regulating hematopoietic lineage development in hESCs.
- VEGF-A165 is a key regulator of erythroid commitment in hESC-derived hematopoiesis.