Characterization of Patient-Derived GNAQ Mutated Endothelial Cells from Capillary Malformations

Capillary malformations (CM) (port-wine stains) are congenital skin lesions that are characterized by dilated capillaries and postcapillary venules. CMs are caused by altered functioning of the vascular endothelium. Somatic genetic mutations have predominantly been identified in the endothelial cell...

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Autores: Langbroek, Ginger Beau|||0000-0002-9801-1415, Stor, Merem L.E.|||0000-0002-4331-9631, Janssen, Vera|||0000-0002-0788-8060, de Haan, Annett, Horbach, Sophie E.R.|||0000-0002-3165-4774, Graupera, Mariona|||0000-0003-4608-4185, van Noesel, Carel J.M.|||0000-0001-7907-7390, van der Horst, Chantal M.A.M.|||0000-0002-4937-3786, Wolkerstorfer, Albert|||0000-0003-1421-1493, Huveneers, Sthephan|||0000-0002-1091-475X
Tipo de recurso: artículo
Fecha de publicación:2023
País:España
Institución:Universitat Autònoma de Barcelona
Repositorio:Dipòsit Digital de Documents de la UAB
Idioma:inglés
OAI Identifier:oai:ddd.uab.cat:289909
Acceso en línea:https://ddd.uab.cat/record/289909
https://dx.doi.org/urn:doi:10.1016/j.jid.2023.10.033
Access Level:acceso abierto
Palabra clave:Angiogenesis
Endothelial cells
Port-wine stains
Sturge-Weber syndrome
Vascular malformations
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spelling Characterization of Patient-Derived GNAQ Mutated Endothelial Cells from Capillary MalformationsLangbroek, Ginger Beau|||0000-0002-9801-1415Stor, Merem L.E.|||0000-0002-4331-9631Janssen, Vera|||0000-0002-0788-8060de Haan, AnnettHorbach, Sophie E.R.|||0000-0002-3165-4774Graupera, Mariona|||0000-0003-4608-4185van Noesel, Carel J.M.|||0000-0001-7907-7390van der Horst, Chantal M.A.M.|||0000-0002-4937-3786Wolkerstorfer, Albert|||0000-0003-1421-1493Huveneers, Sthephan|||0000-0002-1091-475XAngiogenesisEndothelial cellsPort-wine stainsSturge-Weber syndromeVascular malformationsCapillary malformations (CM) (port-wine stains) are congenital skin lesions that are characterized by dilated capillaries and postcapillary venules. CMs are caused by altered functioning of the vascular endothelium. Somatic genetic mutations have predominantly been identified in the endothelial cells of CMs, providing an opportunity for the development of targeted therapies. However, there is currently limited in-depth mechanistic insight into the pathophysiology and a lack of preclinical research approaches. In a monocenter exploratory study of 17 adult patients with CMs, we found somatic sequence variants in the GNAQ (p.R183Q, p.R183G, or p.Q209R) or GNA11 (p.R183C) genes. We applied an endothelial-selective cell isolation protocol to culture primary endothelial cells from skin biopsies from these patients. We successfully expanded patient-derived cells in culture in 3 of the 17 cases while maintaining endothelial specificity as demonstrated by vascular endothelial-cadherin immunostainings. In addition, we tested the angiogenic capacity of endothelial cells from a patient with a GNAQ (p.R183G) sequence substitution. These proof-of-principle results reveal that primary cells isolated from CMs may represent a functional research model to investigate the role of endothelial somatic mutations in the etiology of CMs, but improved isolation and culture methodologies are urgently needed to advance the field. 22023-01-0120232023-01-01Articlehttp://purl.org/coar/resource_type/c_6501VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttps://ddd.uab.cat/record/289909https://dx.doi.org/urn:doi:10.1016/j.jid.2023.10.033reponame:Dipòsit Digital de Documents de la UABinstname:Universitat Autònoma de BarcelonaInglésengopen accesshttp://purl.org/coar/access_right/c_abf2Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.https://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:ddd.uab.cat:2899092026-06-06T12:50:31Z
dc.title.none.fl_str_mv Characterization of Patient-Derived GNAQ Mutated Endothelial Cells from Capillary Malformations
title Characterization of Patient-Derived GNAQ Mutated Endothelial Cells from Capillary Malformations
spellingShingle Characterization of Patient-Derived GNAQ Mutated Endothelial Cells from Capillary Malformations
Langbroek, Ginger Beau|||0000-0002-9801-1415
Angiogenesis
Endothelial cells
Port-wine stains
Sturge-Weber syndrome
Vascular malformations
title_short Characterization of Patient-Derived GNAQ Mutated Endothelial Cells from Capillary Malformations
title_full Characterization of Patient-Derived GNAQ Mutated Endothelial Cells from Capillary Malformations
title_fullStr Characterization of Patient-Derived GNAQ Mutated Endothelial Cells from Capillary Malformations
title_full_unstemmed Characterization of Patient-Derived GNAQ Mutated Endothelial Cells from Capillary Malformations
title_sort Characterization of Patient-Derived GNAQ Mutated Endothelial Cells from Capillary Malformations
dc.creator.none.fl_str_mv Langbroek, Ginger Beau|||0000-0002-9801-1415
Stor, Merem L.E.|||0000-0002-4331-9631
Janssen, Vera|||0000-0002-0788-8060
de Haan, Annett
Horbach, Sophie E.R.|||0000-0002-3165-4774
Graupera, Mariona|||0000-0003-4608-4185
van Noesel, Carel J.M.|||0000-0001-7907-7390
van der Horst, Chantal M.A.M.|||0000-0002-4937-3786
Wolkerstorfer, Albert|||0000-0003-1421-1493
Huveneers, Sthephan|||0000-0002-1091-475X
author Langbroek, Ginger Beau|||0000-0002-9801-1415
author_facet Langbroek, Ginger Beau|||0000-0002-9801-1415
Stor, Merem L.E.|||0000-0002-4331-9631
Janssen, Vera|||0000-0002-0788-8060
de Haan, Annett
Horbach, Sophie E.R.|||0000-0002-3165-4774
Graupera, Mariona|||0000-0003-4608-4185
van Noesel, Carel J.M.|||0000-0001-7907-7390
van der Horst, Chantal M.A.M.|||0000-0002-4937-3786
Wolkerstorfer, Albert|||0000-0003-1421-1493
Huveneers, Sthephan|||0000-0002-1091-475X
author_role author
author2 Stor, Merem L.E.|||0000-0002-4331-9631
Janssen, Vera|||0000-0002-0788-8060
de Haan, Annett
Horbach, Sophie E.R.|||0000-0002-3165-4774
Graupera, Mariona|||0000-0003-4608-4185
van Noesel, Carel J.M.|||0000-0001-7907-7390
van der Horst, Chantal M.A.M.|||0000-0002-4937-3786
Wolkerstorfer, Albert|||0000-0003-1421-1493
Huveneers, Sthephan|||0000-0002-1091-475X
author2_role author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Angiogenesis
Endothelial cells
Port-wine stains
Sturge-Weber syndrome
Vascular malformations
topic Angiogenesis
Endothelial cells
Port-wine stains
Sturge-Weber syndrome
Vascular malformations
description Capillary malformations (CM) (port-wine stains) are congenital skin lesions that are characterized by dilated capillaries and postcapillary venules. CMs are caused by altered functioning of the vascular endothelium. Somatic genetic mutations have predominantly been identified in the endothelial cells of CMs, providing an opportunity for the development of targeted therapies. However, there is currently limited in-depth mechanistic insight into the pathophysiology and a lack of preclinical research approaches. In a monocenter exploratory study of 17 adult patients with CMs, we found somatic sequence variants in the GNAQ (p.R183Q, p.R183G, or p.Q209R) or GNA11 (p.R183C) genes. We applied an endothelial-selective cell isolation protocol to culture primary endothelial cells from skin biopsies from these patients. We successfully expanded patient-derived cells in culture in 3 of the 17 cases while maintaining endothelial specificity as demonstrated by vascular endothelial-cadherin immunostainings. In addition, we tested the angiogenic capacity of endothelial cells from a patient with a GNAQ (p.R183G) sequence substitution. These proof-of-principle results reveal that primary cells isolated from CMs may represent a functional research model to investigate the role of endothelial somatic mutations in the etiology of CMs, but improved isolation and culture methodologies are urgently needed to advance the field.
publishDate 2023
dc.date.none.fl_str_mv 2
2023-01-01
2023
2023-01-01
dc.type.none.fl_str_mv Article
http://purl.org/coar/resource_type/c_6501
VoR
http://purl.org/coar/version/c_970fb48d4fbd8a85
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv https://ddd.uab.cat/record/289909
https://dx.doi.org/urn:doi:10.1016/j.jid.2023.10.033
url https://ddd.uab.cat/record/289909
https://dx.doi.org/urn:doi:10.1016/j.jid.2023.10.033
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
https://creativecommons.org/licenses/by/4.0/
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
https://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
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dc.source.none.fl_str_mv reponame:Dipòsit Digital de Documents de la UAB
instname:Universitat Autònoma de Barcelona
instname_str Universitat Autònoma de Barcelona
reponame_str Dipòsit Digital de Documents de la UAB
collection Dipòsit Digital de Documents de la UAB
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