BMP4 regulates vascular progenitor development in human embryonic stem cells through a Smad-dependent pathway.
The signals that direct pluripotent stem cell differentiation into lineage-specific cells remain largely unknown. Here, we investigated the roles of BMP on vascular progenitor development from human embryonic stem cells (hESCs). In a serum-free condition, hESCs sequentially differentiated into CD34+CD31-, CD34+CD31+, and then CD34-CD31+ cells during vascular cell development. CD34+CD31+ cells contained vascular progenitor population that gives rise to endothelial cells and smooth muscle cells. BMP4 promoted hESC differentiation into CD34+CD31+ cells at an early stage. In contrast, TGFbeta suppressed BMP4-induced CD34+CD31+ cell development, and promoted CD34+CD31- cells that failed to give rise to either endothelial or smooth muscle cells. The BMP-Smad inhibitor, dorsomorphin, inhibited phosphorylation of Smad1/5/8, and blocked hESC differentiation to CD34+CD31+ progenitor cells, suggesting that BMP Smad-dependent signaling is critical for CD34+CD31+ vascular progenitor development. Our findings provide new insight into how pluripotent hESCs differentiate into vascular cells.
Bai
Hao
H
Maine Medical Center, Maine Medical Center Research Institute, Scarborough, Maine 04074, USA.
Gao
Yongxing
Y
Arzigian
Melanie
M
Wojchowski
Don M
DM
Wu
Wen-Shu
WS
Wang
Zack Z
ZZ
D018952:Antigens, CD34; D055415:Bone Morphogenetic Protein 4 / Q000037:antagonists & inhibitors / Q000378:metabolism* / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects* / Q000502:physiology; D002460:Cell Line; D019070:Cell Lineage; D016895:Culture Media, Serum-Free; D053595:Embryonic Stem Cells / Q000166:cytology* / Q000378:metabolism; D042783:Endothelial Cells / Q000166:cytology; D006801:Humans; D009131:Muscle, Smooth, Vascular / Q000166:cytology; D018919:Neovascularization, Physiologic; D010766:Phosphorylation; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D011720:Pyrazoles / Q000494:pharmacology; D011743:Pyrimidines / Q000494:pharmacology; D015398:Signal Transduction; D051785:Smad Proteins / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000494:pharmacology
D018952:Antigens, CD34; C525809:BMP4 protein, human; D055415:Bone Morphogenetic Protein 4; D016895:Culture Media, Serum-Free; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D011720:Pyrazoles; D011743:Pyrimidines; D051785:Smad Proteins; D016212:Transforming Growth Factor beta; C516138:dorsomorphin