Autologous correction in patient induced pluripotent stem cell-endothelial cells to identify a novel pathogenic mutation of hereditary hemorrhagic telangiectasia
Hereditary hemorrhagic telangiectasia is a rare disease with autosomal dominant inheritance. More than 80% hereditary hemorrhagic telangiectasia patients carry heterozygous mutations of Endoglin or Activin receptor-like kinase-1 genes. Endoglin plays important roles in vasculogenesis and human vascu...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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SAGE Publications
2020
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7691931/ https://www.ncbi.nlm.nih.gov/pubmed/33282178 http://dx.doi.org/10.1177/2045894019885357 |
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author | Zhou, Fang Zhao, Xiuli Liu, Xiu Liu, Yanyan Ma, Feng Liu, Bao Yang, Jun |
author_facet | Zhou, Fang Zhao, Xiuli Liu, Xiu Liu, Yanyan Ma, Feng Liu, Bao Yang, Jun |
author_sort | Zhou, Fang |
collection | PubMed |
description | Hereditary hemorrhagic telangiectasia is a rare disease with autosomal dominant inheritance. More than 80% hereditary hemorrhagic telangiectasia patients carry heterozygous mutations of Endoglin or Activin receptor-like kinase-1 genes. Endoglin plays important roles in vasculogenesis and human vascular disease. In this report, we found a novel missense mutation (c.88T > C) of Endoglin gene in a hereditary hemorrhagic telangiectasia 1 patient. Induced pluripotent stem cells of the patient were generated and differentiated into endothelial cells. The hereditary hemorrhagic telangiectasia-induced pluripotent stem cells have reduced differentiation potential toward vascular endothelial cells and defective angiogenesis with impaired tube formation. Endoplasmic reticulum retention of the mutant Endoglin (Cys30Arg, C30R) causes less functional protein trafficking to cell surface, which contributes to the pathogenesis of hereditary hemorrhagic telangiectasia. Clustered Regularly Interspaced Short Palindromic Repeats/Cas9 genetic correction of the c.88T > C mutation in induced pluripotent stem cells revealed that C30R mutation of Endoglin affects bone morphogenetic protein 9 downstream signaling. By establishing a human induced pluripotent stem cell from hereditary hemorrhagic telangiectasia patient peripheral blood mononuclear cells and autologous correction on mutant hereditary hemorrhagic telangiectasia-induced pluripotent stem cells, we were able to identify a new disease-causing mutation, which facilitates us to understand the roles of Endoglin in vascular development and pathogenesis of related vascular diseases. |
format | Online Article Text |
id | pubmed-7691931 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | SAGE Publications |
record_format | MEDLINE/PubMed |
spelling | pubmed-76919312020-12-04 Autologous correction in patient induced pluripotent stem cell-endothelial cells to identify a novel pathogenic mutation of hereditary hemorrhagic telangiectasia Zhou, Fang Zhao, Xiuli Liu, Xiu Liu, Yanyan Ma, Feng Liu, Bao Yang, Jun Pulm Circ Original Research Article Hereditary hemorrhagic telangiectasia is a rare disease with autosomal dominant inheritance. More than 80% hereditary hemorrhagic telangiectasia patients carry heterozygous mutations of Endoglin or Activin receptor-like kinase-1 genes. Endoglin plays important roles in vasculogenesis and human vascular disease. In this report, we found a novel missense mutation (c.88T > C) of Endoglin gene in a hereditary hemorrhagic telangiectasia 1 patient. Induced pluripotent stem cells of the patient were generated and differentiated into endothelial cells. The hereditary hemorrhagic telangiectasia-induced pluripotent stem cells have reduced differentiation potential toward vascular endothelial cells and defective angiogenesis with impaired tube formation. Endoplasmic reticulum retention of the mutant Endoglin (Cys30Arg, C30R) causes less functional protein trafficking to cell surface, which contributes to the pathogenesis of hereditary hemorrhagic telangiectasia. Clustered Regularly Interspaced Short Palindromic Repeats/Cas9 genetic correction of the c.88T > C mutation in induced pluripotent stem cells revealed that C30R mutation of Endoglin affects bone morphogenetic protein 9 downstream signaling. By establishing a human induced pluripotent stem cell from hereditary hemorrhagic telangiectasia patient peripheral blood mononuclear cells and autologous correction on mutant hereditary hemorrhagic telangiectasia-induced pluripotent stem cells, we were able to identify a new disease-causing mutation, which facilitates us to understand the roles of Endoglin in vascular development and pathogenesis of related vascular diseases. SAGE Publications 2020-11-25 /pmc/articles/PMC7691931/ /pubmed/33282178 http://dx.doi.org/10.1177/2045894019885357 Text en © The Author(s) 2020 https://creativecommons.org/licenses/by-nc/4.0/ Creative Commons Non Commercial CC BY-NC: This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License (https://creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages (https://us.sagepub.com/en-us/nam/open-access-at-sage). |
spellingShingle | Original Research Article Zhou, Fang Zhao, Xiuli Liu, Xiu Liu, Yanyan Ma, Feng Liu, Bao Yang, Jun Autologous correction in patient induced pluripotent stem cell-endothelial cells to identify a novel pathogenic mutation of hereditary hemorrhagic telangiectasia |
title | Autologous correction in patient induced pluripotent stem cell-endothelial
cells to identify a novel pathogenic mutation of hereditary hemorrhagic
telangiectasia |
title_full | Autologous correction in patient induced pluripotent stem cell-endothelial
cells to identify a novel pathogenic mutation of hereditary hemorrhagic
telangiectasia |
title_fullStr | Autologous correction in patient induced pluripotent stem cell-endothelial
cells to identify a novel pathogenic mutation of hereditary hemorrhagic
telangiectasia |
title_full_unstemmed | Autologous correction in patient induced pluripotent stem cell-endothelial
cells to identify a novel pathogenic mutation of hereditary hemorrhagic
telangiectasia |
title_short | Autologous correction in patient induced pluripotent stem cell-endothelial
cells to identify a novel pathogenic mutation of hereditary hemorrhagic
telangiectasia |
title_sort | autologous correction in patient induced pluripotent stem cell-endothelial
cells to identify a novel pathogenic mutation of hereditary hemorrhagic
telangiectasia |
topic | Original Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7691931/ https://www.ncbi.nlm.nih.gov/pubmed/33282178 http://dx.doi.org/10.1177/2045894019885357 |
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