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, Maria 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; Mesri, Enrique Alfredo
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.
Fil: Naipauer, Julian. Miami University; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Sylvester Comprehensive Cancer Center and Miami Center for AIDS Research; Estados Unidos
Fil: Rosario, Santas. Miami University; Estados Unidos. Sylvester Comprehensive Cancer Center and Miami Center for AIDS Research; Estados Unidos
Fil: Gupta, Sachin. Miami University; Estados Unidos. Sylvester Comprehensive Cancer Center and Miami Center for AIDS Research; Estados Unidos
Fil: Premer, Courtney. Miami University; Estados Unidos
Fil: Méndez Solís, Omayra. Miami University; Estados Unidos. Sylvester Comprehensive Cancer Center and Miami Center for AIDS Research; Estados Unidos
Fil: Schlesinger, Mariana. Miami University; Estados Unidos. Sylvester Comprehensive Cancer Center and Miami Center for AIDS Research; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Ponzinibbio, Maria Virginia. Miami University; Estados Unidos. Sylvester Comprehensive Cancer Center and Miami Center for AIDS Research; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Jain, Vaibhav. University of Florida; Estados Unidos
Fil: Gay, Lauren. University of Florida; Estados Unidos
Fil: Renne, Rolf. University of Florida; Estados Unidos
Fil: Chan, Ho Lam. Miami University; Estados Unidos
Fil: Morey, Lluis. Miami University; Estados Unidos
Fil: Salyakina, Daria. Miami University; Estados Unidos. Sylvester Comprehensive Cancer Center and Miami Center for AIDS Research; Estados Unidos
Fil: Abba, Martín Carlos. Miami University; Estados Unidos. Universidad Nacional de La Plata. Facultad de Ciencias Médicas. Centro de Investigaciones Inmunológicas Básicas y Aplicadas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Williams, Sion. Miami University; Estados Unidos
Fil: Hare, Joshua M.. Miami University; Estados Unidos
Fil: Goldschmidt Clermont, Pascal. Miami University; Estados Unidos
Fil: Mesri, Enrique Alfredo. Sylvester Comprehensive Cancer Center and Miami Center for AIDS Research; Estados Unidos. Miami University; Estados Unidos
Materia
KSHV
PDGFRA
Mesenchymal stem cell
Angiogenic environment
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/126251
Acceder
id CONICETDig_741e87c76eb7e6befa09cf594c49e190
oai_identifier_str oai:ri.conicet.gov.ar:11336/126251
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
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, Maria VirginiaJain, VaibhavGay, LaurenRenne, RolfChan, Ho LamMorey, LluisSalyakina, DariaAbba, Martín CarlosWilliams, SionHare, Joshua M.Goldschmidt Clermont, PascalMesri, Enrique AlfredoKSHVPDGFRAMesenchymal stem cellAngiogenic environmenthttps://purl.org/becyt/ford/3.3https://purl.org/becyt/ford/3Kaposi’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.Fil: Naipauer, Julian. Miami University; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Sylvester Comprehensive Cancer Center and Miami Center for AIDS Research; Estados UnidosFil: Rosario, Santas. Miami University; Estados Unidos. Sylvester Comprehensive Cancer Center and Miami Center for AIDS Research; Estados UnidosFil: Gupta, Sachin. Miami University; Estados Unidos. Sylvester Comprehensive Cancer Center and Miami Center for AIDS Research; Estados UnidosFil: Premer, Courtney. Miami University; Estados UnidosFil: Méndez Solís, Omayra. Miami University; Estados Unidos. Sylvester Comprehensive Cancer Center and Miami Center for AIDS Research; Estados UnidosFil: Schlesinger, Mariana. Miami University; Estados Unidos. Sylvester Comprehensive Cancer Center and Miami Center for AIDS Research; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Ponzinibbio, Maria Virginia. Miami University; Estados Unidos. Sylvester Comprehensive Cancer Center and Miami Center for AIDS Research; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Jain, Vaibhav. University of Florida; Estados UnidosFil: Gay, Lauren. University of Florida; Estados UnidosFil: Renne, Rolf. University of Florida; Estados UnidosFil: Chan, Ho Lam. Miami University; Estados UnidosFil: Morey, Lluis. Miami University; Estados UnidosFil: Salyakina, Daria. Miami University; Estados Unidos. Sylvester Comprehensive Cancer Center and Miami Center for AIDS Research; Estados UnidosFil: Abba, Martín Carlos. Miami University; Estados Unidos. Universidad Nacional de La Plata. Facultad de Ciencias Médicas. Centro de Investigaciones Inmunológicas Básicas y Aplicadas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Williams, Sion. Miami University; Estados UnidosFil: Hare, Joshua M.. Miami University; Estados UnidosFil: Goldschmidt Clermont, Pascal. Miami University; Estados UnidosFil: Mesri, Enrique Alfredo. Sylvester Comprehensive Cancer Center and Miami Center for AIDS Research; Estados Unidos. Miami University; Estados UnidosPublic Library of Science2019-12-27info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/126251Naipauer, Julian; Rosario, Santas; Gupta, Sachin; Premer, Courtney; Méndez Solís, Omayra; et al.; PDGFRA defines the mesenchymal stem cell Kaposi's sarcoma progenitors by enabling KSHV oncogenesis in an angiogenic environment; Public Library of Science; Plos Pathogens; 15; 12; 27-12-2019; 1-381553-73661553-7374CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://dx.plos.org/10.1371/journal.ppat.1008221info:eu-repo/semantics/altIdentifier/doi/10.1371/journal.ppat.1008221info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T09:53:17Zoai:ri.conicet.gov.ar:11336/126251instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-03 09:53:17.709CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
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
KSHV
PDGFRA
Mesenchymal stem cell
Angiogenic environment
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, Maria 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
Mesri, Enrique Alfredo
author Naipauer, Julian
author_facet Naipauer, Julian
Rosario, Santas
Gupta, Sachin
Premer, Courtney
Méndez Solís, Omayra
Schlesinger, Mariana
Ponzinibbio, Maria 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
Mesri, Enrique Alfredo
author_role author
author2 Rosario, Santas
Gupta, Sachin
Premer, Courtney
Méndez Solís, Omayra
Schlesinger, Mariana
Ponzinibbio, Maria 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
Mesri, Enrique Alfredo
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 KSHV
PDGFRA
Mesenchymal stem cell
Angiogenic environment
topic KSHV
PDGFRA
Mesenchymal stem cell
Angiogenic environment
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.3
https://purl.org/becyt/ford/3
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.
Fil: Naipauer, Julian. Miami University; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Sylvester Comprehensive Cancer Center and Miami Center for AIDS Research; Estados Unidos
Fil: Rosario, Santas. Miami University; Estados Unidos. Sylvester Comprehensive Cancer Center and Miami Center for AIDS Research; Estados Unidos
Fil: Gupta, Sachin. Miami University; Estados Unidos. Sylvester Comprehensive Cancer Center and Miami Center for AIDS Research; Estados Unidos
Fil: Premer, Courtney. Miami University; Estados Unidos
Fil: Méndez Solís, Omayra. Miami University; Estados Unidos. Sylvester Comprehensive Cancer Center and Miami Center for AIDS Research; Estados Unidos
Fil: Schlesinger, Mariana. Miami University; Estados Unidos. Sylvester Comprehensive Cancer Center and Miami Center for AIDS Research; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Ponzinibbio, Maria Virginia. Miami University; Estados Unidos. Sylvester Comprehensive Cancer Center and Miami Center for AIDS Research; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Jain, Vaibhav. University of Florida; Estados Unidos
Fil: Gay, Lauren. University of Florida; Estados Unidos
Fil: Renne, Rolf. University of Florida; Estados Unidos
Fil: Chan, Ho Lam. Miami University; Estados Unidos
Fil: Morey, Lluis. Miami University; Estados Unidos
Fil: Salyakina, Daria. Miami University; Estados Unidos. Sylvester Comprehensive Cancer Center and Miami Center for AIDS Research; Estados Unidos
Fil: Abba, Martín Carlos. Miami University; Estados Unidos. Universidad Nacional de La Plata. Facultad de Ciencias Médicas. Centro de Investigaciones Inmunológicas Básicas y Aplicadas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Williams, Sion. Miami University; Estados Unidos
Fil: Hare, Joshua M.. Miami University; Estados Unidos
Fil: Goldschmidt Clermont, Pascal. Miami University; Estados Unidos
Fil: Mesri, Enrique Alfredo. Sylvester Comprehensive Cancer Center and Miami Center for AIDS Research; Estados Unidos. Miami University; Estados Unidos
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 2019-12-27
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
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://hdl.handle.net/11336/126251
Naipauer, Julian; Rosario, Santas; Gupta, Sachin; Premer, Courtney; Méndez Solís, Omayra; et al.; PDGFRA defines the mesenchymal stem cell Kaposi's sarcoma progenitors by enabling KSHV oncogenesis in an angiogenic environment; Public Library of Science; Plos Pathogens; 15; 12; 27-12-2019; 1-38
1553-7366
1553-7374
CONICET Digital
CONICET
url http://hdl.handle.net/11336/126251
identifier_str_mv Naipauer, Julian; Rosario, Santas; Gupta, Sachin; Premer, Courtney; Méndez Solís, Omayra; et al.; PDGFRA defines the mesenchymal stem cell Kaposi's sarcoma progenitors by enabling KSHV oncogenesis in an angiogenic environment; Public Library of Science; Plos Pathogens; 15; 12; 27-12-2019; 1-38
1553-7366
1553-7374
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://dx.plos.org/10.1371/journal.ppat.1008221
info:eu-repo/semantics/altIdentifier/doi/10.1371/journal.ppat.1008221
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv Public Library of Science
publisher.none.fl_str_mv Public Library of Science
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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score 13.13397

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