In this section
@inproceedings{Foldes:2018:cvr/cvy060.108,
author = {Foldes, G and Lawlor, K and Harding, SE and Randi, AM},
doi = {cvr/cvy060.108},
pages = {S39--S39},
publisher = {OXFORD UNIV PRESS},
title = {STAT3 mediates differentiation and maintenance of human pluripotent stem-derived endothelial cells},
url = {http://dx.doi.org/10.1093/cvr/cvy060.108},
year = {2018}
}
TY - CPAPER
AB - Background: High plasticity derivatives of human pluripotent stem cells (hPSC) such as embryonic stem cells (hESC) are being intensively developed for their use in endothelial replacement.Methods/Results: In this study, we found that transient addition of Activin A, followed by culture with VEGF165, BMP4 and FGF2 was an effective mechanism to induce differentiation of hESC toward the endothelial lineage. Indeed, human GeneChip microarray analysis revealed that endothelial gene regulatory networks were gradually increased during 12 days of differentiation. Isolated hESC-derived endothelial cells (hESC-EC) expressed mature endothelial-associated genes, including CD31, NRP1, VE-cadherin, Tie2, VWF and ICAM2, reaching levels comparable with human umbilical cord vascular endothelial cells by day 19. We found that a network of CD31+ tubes comprising endothelial precursor cells had formed in culture from 10 days after start of differentiation of hESC. As assessed by automated high content microscopy, the alignment and tube formation of the newly formed CD31+ vascular network were markedly decreased in response to C188-9, a novel small molecule inhibitor of STAT3 transcription factor (tube length: 57%, connected tube area: 22% of those in control, both p<0.001). Human ESC-EC were capable of transdifferentiating into mesenchymal cells in long-term cultures. Endothelial-mesenchymal transition was characterised by gradual loss of endothelial marker expression and increased mesenchymal marker FSP1 expression. We found that inhibition of STAT3 tyr705 phosphorylation by C188-9 resulted in a decreased proliferation of FSP1+ mesenchymal cells (2-fold decrease in Ki67%-positive population, p<0.001), and subsequently reduced number of FSP+ cells (36% reduction, p<0.05). At the same time, C188-9 increased the number of CD31+ hESC-EC by 30% (p=0.05, n=6). Viability remained unchanged in C188-9-treated cells (Topro3 necrosis marker, p=0.32, n=3).Conclusions: These results sugge
AU - Foldes,G
AU - Lawlor,K
AU - Harding,SE
AU - Randi,AM
DO - cvr/cvy060.108
EP - 39
PB - OXFORD UNIV PRESS
PY - 2018///
SN - 0008-6363
SP - 39
TI - STAT3 mediates differentiation and maintenance of human pluripotent stem-derived endothelial cells
UR - http://dx.doi.org/10.1093/cvr/cvy060.108
UR - http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000430678500110&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
UR - http://hdl.handle.net/10044/1/60143
ER -