VEGF-A165 augments erythropoietic development from human embryonic stem cells.
Combinations of hematopoietic cytokines and the ventral mesoderm inducer BMP-4 have recently been shown to augment hematopoietic cell fate of human embryonic stem cells (hESCs) during embryoid body (EB) development. However, factors capable of regulating lineage commitment of hESC-derived hematopoiesis have yet to be reported. Here we show that vascular endothelial growth factor (VEGF-A165) selectively promotes erythropoietic development from hESCs. Effects of VEGF-A165 were dependent on the presence of hematopoietic cytokines and BMP-4, and could be augmented by addition of erythropoietin (EPO). Treatment of human EBs with VEGF-A165 increased the frequency of cells coexpressing CD34 and the VEGF-A165 receptor KDR, as well as cells expressing erythroid markers. Although fetal/adult globins were unaffected, VEGF-A165 induced the expression of embryonic zeta (zeta) and epsilon (epsilon) globins, and was accompanied by expression of the hematopoietic transcription factor SCL/Tal-1. In addition to promoting erythropoietic differentiation from hESCs, the presence of VEGF-A165 enhanced the in vitro self-renewal potential of primitive hematopoietic cells capable of erythroid progenitor capacity. Our study demonstrates a role for VEGF-A165 during erythropoiesis of differentiating hESCs, thereby providing the first evidence for a factor capable of regulating hematopoietic lineage development of hESCs.
Cerdan
Chantal
C
Robarts Research Institute, Stem Cell Biology and Regenerative Medicine, The University of Western Ontario, London, ON, Canada.
Rouleau
Anne
A
Bhatia
Mickie
M
D002454:Cell Differentiation; D002478:Cells, Cultured; D003114:Colony-Forming Units Assay; D017931:DNA Primers; D004920:Erythropoiesis / Q000187:drug effects / Q000502:physiology*; D005914:Globins / Q000235:genetics; D006801:Humans; D039904:Pluripotent Stem Cells / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D020033:Protein Isoforms / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D042461:Vascular Endothelial Growth Factor A / Q000494:pharmacology*
D017931:DNA Primers; D020033:Protein Isoforms; D042461:Vascular Endothelial Growth Factor A; D005914:Globins