PDGFRA defines the mesenchymal stem cell Kaposi's sarcoma progenitors by enabling KSHV oncogenesis in an angiogenic environment

Autores
Naipauer, Julian; Rosario, Santas; Gupta, Sachin; Premer, Courtney; Méndez-Solís, Omayra; Schlesinger, Mariana; Ponzinibbio, María Virginia; Jain, Vaibhav; Gay, Lauren; Renne, Rolf; Chan, Ho Lam; Morey, Lluis; Salyakina, Daria; Abba, Martín Carlos; Williams, Sion; Hare, Joshua M.; Goldschmidt-Clermont, Pascal J.; Mesri, Enrique A.
Año de publicación
2019
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Kaposi’s sarcoma (KS) is an AIDS-defining cancer caused by the KS-associated herpesvirus (KSHV). Unanswered questions regarding KS are its cellular ontology and the conditions conducive to viral oncogenesis. We identify PDGFRA(+)/SCA-1(+) bone marrow-derived mesenchymal stem cells (Pα(+)S MSCs) as KS spindle-cell progenitors and found that pro-angiogenic environmental conditions typical of KS are critical for KSHV sarcomagenesis. This is because growth in KS-like conditions generates a de-repressed KSHV epigenome allowing oncogenic KSHV gene expression in infected Pα(+)S MSCs. Furthermore, these growth conditions allow KSHV-infected Pα(+)S MSCs to overcome KSHV-driven oncogene-induced senescence and cell cycle arrest via a PDGFRA-signaling mechanism; thus identifying PDGFRA not only as a phenotypic determinant for KS-progenitors but also as a critical enabler for viral oncogenesis.
Centro de Investigaciones Inmunológicas Básicas y Aplicadas
Materia
Biología
Ciencias Médicas
Mesenchymal stem cells
Gene expression
Cancers and neoplasms
Carcinogenesis
Kaposi sarcoma
Nivel de accesibilidad
acceso abierto
Condiciones de uso
http://creativecommons.org/licenses/by/4.0/
Repositorio
SEDICI (UNLP)
Institución
Universidad Nacional de La Plata
OAI Identificador
oai:sedici.unlp.edu.ar:10915/107504
Acceder
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oai_identifier_str oai:sedici.unlp.edu.ar:10915/107504
network_acronym_str SEDICI
repository_id_str 1329
network_name_str SEDICI (UNLP)
spelling PDGFRA defines the mesenchymal stem cell Kaposi's sarcoma progenitors by enabling KSHV oncogenesis in an angiogenic environmentNaipauer, JulianRosario, SantasGupta, SachinPremer, CourtneyMéndez-Solís, OmayraSchlesinger, MarianaPonzinibbio, María VirginiaJain, VaibhavGay, LaurenRenne, RolfChan, Ho LamMorey, LluisSalyakina, DariaAbba, Martín CarlosWilliams, SionHare, Joshua M.Goldschmidt-Clermont, Pascal J.Mesri, Enrique A.BiologíaCiencias MédicasMesenchymal stem cellsGene expressionCancers and neoplasmsCarcinogenesisKaposi sarcomaKaposi’s sarcoma (KS) is an AIDS-defining cancer caused by the KS-associated herpesvirus (KSHV). Unanswered questions regarding KS are its cellular ontology and the conditions conducive to viral oncogenesis. We identify PDGFRA(+)/SCA-1(+) bone marrow-derived mesenchymal stem cells (Pα(+)S MSCs) as KS spindle-cell progenitors and found that pro-angiogenic environmental conditions typical of KS are critical for KSHV sarcomagenesis. This is because growth in KS-like conditions generates a de-repressed KSHV epigenome allowing oncogenic KSHV gene expression in infected Pα(+)S MSCs. Furthermore, these growth conditions allow KSHV-infected Pα(+)S MSCs to overcome KSHV-driven oncogene-induced senescence and cell cycle arrest via a PDGFRA-signaling mechanism; thus identifying PDGFRA not only as a phenotypic determinant for KS-progenitors but also as a critical enabler for viral oncogenesis.Centro de Investigaciones Inmunológicas Básicas y Aplicadas2019info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionArticulohttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfhttp://sedici.unlp.edu.ar/handle/10915/107504enginfo:eu-repo/semantics/altIdentifier/url/http://europepmc.org/backend/ptpmcrender.fcgi?accid=PMC6980685&blobtype=pdfinfo:eu-repo/semantics/altIdentifier/issn/1553-7374info:eu-repo/semantics/altIdentifier/pmid/31881074info:eu-repo/semantics/altIdentifier/doi/10.1371/journal.ppat.1008221info:eu-repo/semantics/openAccesshttp://creativecommons.org/licenses/by/4.0/Creative Commons Attribution 4.0 International (CC BY 4.0)reponame:SEDICI (UNLP)instname:Universidad Nacional de La Platainstacron:UNLP2025-09-03T10:56:07Zoai:sedici.unlp.edu.ar:10915/107504Institucionalhttp://sedici.unlp.edu.ar/Universidad públicaNo correspondehttp://sedici.unlp.edu.ar/oai/snrdalira@sedici.unlp.edu.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:13292025-09-03 10:56:07.719SEDICI (UNLP) - Universidad Nacional de La Platafalse
dc.title.none.fl_str_mv PDGFRA defines the mesenchymal stem cell Kaposi's sarcoma progenitors by enabling KSHV oncogenesis in an angiogenic environment
title PDGFRA defines the mesenchymal stem cell Kaposi's sarcoma progenitors by enabling KSHV oncogenesis in an angiogenic environment
spellingShingle PDGFRA defines the mesenchymal stem cell Kaposi's sarcoma progenitors by enabling KSHV oncogenesis in an angiogenic environment
Naipauer, Julian
Biología
Ciencias Médicas
Mesenchymal stem cells
Gene expression
Cancers and neoplasms
Carcinogenesis
Kaposi sarcoma
title_short PDGFRA defines the mesenchymal stem cell Kaposi's sarcoma progenitors by enabling KSHV oncogenesis in an angiogenic environment
title_full PDGFRA defines the mesenchymal stem cell Kaposi's sarcoma progenitors by enabling KSHV oncogenesis in an angiogenic environment
title_fullStr PDGFRA defines the mesenchymal stem cell Kaposi's sarcoma progenitors by enabling KSHV oncogenesis in an angiogenic environment
title_full_unstemmed PDGFRA defines the mesenchymal stem cell Kaposi's sarcoma progenitors by enabling KSHV oncogenesis in an angiogenic environment
title_sort PDGFRA defines the mesenchymal stem cell Kaposi's sarcoma progenitors by enabling KSHV oncogenesis in an angiogenic environment
dc.creator.none.fl_str_mv Naipauer, Julian
Rosario, Santas
Gupta, Sachin
Premer, Courtney
Méndez-Solís, Omayra
Schlesinger, Mariana
Ponzinibbio, María Virginia
Jain, Vaibhav
Gay, Lauren
Renne, Rolf
Chan, Ho Lam
Morey, Lluis
Salyakina, Daria
Abba, Martín Carlos
Williams, Sion
Hare, Joshua M.
Goldschmidt-Clermont, Pascal J.
Mesri, Enrique A.
author Naipauer, Julian
author_facet Naipauer, Julian
Rosario, Santas
Gupta, Sachin
Premer, Courtney
Méndez-Solís, Omayra
Schlesinger, Mariana
Ponzinibbio, María Virginia
Jain, Vaibhav
Gay, Lauren
Renne, Rolf
Chan, Ho Lam
Morey, Lluis
Salyakina, Daria
Abba, Martín Carlos
Williams, Sion
Hare, Joshua M.
Goldschmidt-Clermont, Pascal J.
Mesri, Enrique A.
author_role author
author2 Rosario, Santas
Gupta, Sachin
Premer, Courtney
Méndez-Solís, Omayra
Schlesinger, Mariana
Ponzinibbio, María Virginia
Jain, Vaibhav
Gay, Lauren
Renne, Rolf
Chan, Ho Lam
Morey, Lluis
Salyakina, Daria
Abba, Martín Carlos
Williams, Sion
Hare, Joshua M.
Goldschmidt-Clermont, Pascal J.
Mesri, Enrique A.
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Biología
Ciencias Médicas
Mesenchymal stem cells
Gene expression
Cancers and neoplasms
Carcinogenesis
Kaposi sarcoma
topic Biología
Ciencias Médicas
Mesenchymal stem cells
Gene expression
Cancers and neoplasms
Carcinogenesis
Kaposi sarcoma
dc.description.none.fl_txt_mv Kaposi’s sarcoma (KS) is an AIDS-defining cancer caused by the KS-associated herpesvirus (KSHV). Unanswered questions regarding KS are its cellular ontology and the conditions conducive to viral oncogenesis. We identify PDGFRA(+)/SCA-1(+) bone marrow-derived mesenchymal stem cells (Pα(+)S MSCs) as KS spindle-cell progenitors and found that pro-angiogenic environmental conditions typical of KS are critical for KSHV sarcomagenesis. This is because growth in KS-like conditions generates a de-repressed KSHV epigenome allowing oncogenic KSHV gene expression in infected Pα(+)S MSCs. Furthermore, these growth conditions allow KSHV-infected Pα(+)S MSCs to overcome KSHV-driven oncogene-induced senescence and cell cycle arrest via a PDGFRA-signaling mechanism; thus identifying PDGFRA not only as a phenotypic determinant for KS-progenitors but also as a critical enabler for viral oncogenesis.
Centro de Investigaciones Inmunológicas Básicas y Aplicadas
description Kaposi’s sarcoma (KS) is an AIDS-defining cancer caused by the KS-associated herpesvirus (KSHV). Unanswered questions regarding KS are its cellular ontology and the conditions conducive to viral oncogenesis. We identify PDGFRA(+)/SCA-1(+) bone marrow-derived mesenchymal stem cells (Pα(+)S MSCs) as KS spindle-cell progenitors and found that pro-angiogenic environmental conditions typical of KS are critical for KSHV sarcomagenesis. This is because growth in KS-like conditions generates a de-repressed KSHV epigenome allowing oncogenic KSHV gene expression in infected Pα(+)S MSCs. Furthermore, these growth conditions allow KSHV-infected Pα(+)S MSCs to overcome KSHV-driven oncogene-induced senescence and cell cycle arrest via a PDGFRA-signaling mechanism; thus identifying PDGFRA not only as a phenotypic determinant for KS-progenitors but also as a critical enabler for viral oncogenesis.
publishDate 2019
dc.date.none.fl_str_mv 2019
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
Articulo
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://sedici.unlp.edu.ar/handle/10915/107504
url http://sedici.unlp.edu.ar/handle/10915/107504
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/http://europepmc.org/backend/ptpmcrender.fcgi?accid=PMC6980685&blobtype=pdf
info:eu-repo/semantics/altIdentifier/issn/1553-7374
info:eu-repo/semantics/altIdentifier/pmid/31881074
info:eu-repo/semantics/altIdentifier/doi/10.1371/journal.ppat.1008221
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
http://creativecommons.org/licenses/by/4.0/
Creative Commons Attribution 4.0 International (CC BY 4.0)
eu_rights_str_mv openAccess
rights_invalid_str_mv http://creativecommons.org/licenses/by/4.0/
Creative Commons Attribution 4.0 International (CC BY 4.0)
dc.format.none.fl_str_mv application/pdf
dc.source.none.fl_str_mv reponame:SEDICI (UNLP)
instname:Universidad Nacional de La Plata
instacron:UNLP
reponame_str SEDICI (UNLP)
collection SEDICI (UNLP)
instname_str Universidad Nacional de La Plata
instacron_str UNLP
institution UNLP
repository.name.fl_str_mv SEDICI (UNLP) - Universidad Nacional de La Plata
repository.mail.fl_str_mv alira@sedici.unlp.edu.ar
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