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Sex-dependent VEGF expression underlies variations in human pluripotent stem cell to endothelial progenitor differentiation

Human pluripotent stem cells (hPSCs) offer tremendous promise in tissue engineering and cell-based therapies because of their unique combination of two properties: pluripotency and a high proliferative capacity. To realize this potential, development of efficient hPSC differentiation protocols is re...

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Autores principales: Randolph, Lauren N., Bao, Xiaoping, Oddo, Michael, Lian, Xiaojun Lance
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6853961/
https://www.ncbi.nlm.nih.gov/pubmed/31723192
http://dx.doi.org/10.1038/s41598-019-53054-z
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author Randolph, Lauren N.
Bao, Xiaoping
Oddo, Michael
Lian, Xiaojun Lance
author_facet Randolph, Lauren N.
Bao, Xiaoping
Oddo, Michael
Lian, Xiaojun Lance
author_sort Randolph, Lauren N.
collection PubMed
description Human pluripotent stem cells (hPSCs) offer tremendous promise in tissue engineering and cell-based therapies because of their unique combination of two properties: pluripotency and a high proliferative capacity. To realize this potential, development of efficient hPSC differentiation protocols is required. In this work, sex-based differences are identified in a GSK3 inhibitor based endothelial progenitor differentiation protocol. While male hPSCs efficiently differentiate into CD34 (+ )CD31(+) endothelial progenitors upon GSK3 inhibition, female hPSCs showed limited differentiation capacity using this protocol. Using VE-cadherin-GFP knockin reporter cells, female cells showed significantly increased differentiation efficiency when treated with VEGF during the second stage of endothelial progenitor differentiation. Interestingly, male cells showed no significant change in differentiation efficiency with VEGF treatment, but did show augmented early activation of VE-cadherin expression. A sex-based difference in endogenous expression of VEGF was identified that is likely the underlying cause of discrepancies in sex-dependent differentiation efficiency. These findings highlight the importance of sex differences in progenitor biology and the development of new stem cell differentiation protocols.
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spelling pubmed-68539612019-11-19 Sex-dependent VEGF expression underlies variations in human pluripotent stem cell to endothelial progenitor differentiation Randolph, Lauren N. Bao, Xiaoping Oddo, Michael Lian, Xiaojun Lance Sci Rep Article Human pluripotent stem cells (hPSCs) offer tremendous promise in tissue engineering and cell-based therapies because of their unique combination of two properties: pluripotency and a high proliferative capacity. To realize this potential, development of efficient hPSC differentiation protocols is required. In this work, sex-based differences are identified in a GSK3 inhibitor based endothelial progenitor differentiation protocol. While male hPSCs efficiently differentiate into CD34 (+ )CD31(+) endothelial progenitors upon GSK3 inhibition, female hPSCs showed limited differentiation capacity using this protocol. Using VE-cadherin-GFP knockin reporter cells, female cells showed significantly increased differentiation efficiency when treated with VEGF during the second stage of endothelial progenitor differentiation. Interestingly, male cells showed no significant change in differentiation efficiency with VEGF treatment, but did show augmented early activation of VE-cadherin expression. A sex-based difference in endogenous expression of VEGF was identified that is likely the underlying cause of discrepancies in sex-dependent differentiation efficiency. These findings highlight the importance of sex differences in progenitor biology and the development of new stem cell differentiation protocols. Nature Publishing Group UK 2019-11-13 /pmc/articles/PMC6853961/ /pubmed/31723192 http://dx.doi.org/10.1038/s41598-019-53054-z Text en © The Author(s) 2019 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Randolph, Lauren N.
Bao, Xiaoping
Oddo, Michael
Lian, Xiaojun Lance
Sex-dependent VEGF expression underlies variations in human pluripotent stem cell to endothelial progenitor differentiation
title Sex-dependent VEGF expression underlies variations in human pluripotent stem cell to endothelial progenitor differentiation
title_full Sex-dependent VEGF expression underlies variations in human pluripotent stem cell to endothelial progenitor differentiation
title_fullStr Sex-dependent VEGF expression underlies variations in human pluripotent stem cell to endothelial progenitor differentiation
title_full_unstemmed Sex-dependent VEGF expression underlies variations in human pluripotent stem cell to endothelial progenitor differentiation
title_short Sex-dependent VEGF expression underlies variations in human pluripotent stem cell to endothelial progenitor differentiation
title_sort sex-dependent vegf expression underlies variations in human pluripotent stem cell to endothelial progenitor differentiation
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6853961/
https://www.ncbi.nlm.nih.gov/pubmed/31723192
http://dx.doi.org/10.1038/s41598-019-53054-z
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