期刊
NATURE CELL BIOLOGY
卷 17, 期 8, 页码 994-U294出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/ncb3205
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资金
- Roche Postdoctoral Fellowships (RPF)
- Innovative Medicines Initiative Joint Undertaking [115439]
- European Union
- EFPIA companies
- Swiss National Science Foundation
- German Cancer Aid
- HHMI
- NIH [R01 HL04880, 5P30 DK49216, 5R01 DK53298, 5U01 HL10001-05, R24 DK092760, HL106018, HL083867, HL60963, 2R01DK081572, R01DK097768, U01HL100408]
- Harvard Stem Cell Institute and Harvard University
- NATIONAL HEART, LUNG, AND BLOOD INSTITUTE [U01HL100408, R01HL048801, R01HL083867, R01HL106018] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES [R01DK097768, R01DK053298, R01DK081572, P30DK049216, R24DK092760] Funding Source: NIH RePORTER
The use of human pluripotent stem cells for in vitro disease modelling and clinical applications requires protocols that convert these cells into relevant adult cell types. Here, we report the rapid and efficient differentiation of human pluripotent stem cells into vascular endothelial and smooth muscle cells. We found that GSK3 inhibition and BMP4 treatment rapidly committed pluripotent cells to a mesodermal fate and subsequent exposure to VEGF-A or PDGF-BB resulted in the differentiation of either endothelial or vascular smooth muscle cells, respectively. Both protocols produced mature cells with efficiencies exceeding 80% within six days. On purification to 99% via surface markers, endothelial cells maintained their identity, as assessed by marker gene expression, and showed relevant in vitro and in vivo functionality. Global transcriptional and metabolomic analyses confirmed that the cells closely resembled their in vivo counterparts. Our results suggest that these cells could be used to faithfully model human disease.
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