PDGFRA defines the mesenchymal stem cell Kaposi's sarcoma progenitors by enabling KSHV oncogenesis in an angiogenic environment.
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)...
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2019-12-01
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| Series: | PLoS Pathogens |
| Online Access: | https://journals.plos.org/plospathogens/article/file?id=10.1371/journal.ppat.1008221&type=printable |
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| author | Julian Naipauer Santas Rosario Sachin Gupta Courtney Premer Omayra Méndez-Solís Mariana Schlesinger Virginia Ponzinibbio Vaibhav Jain Lauren Gay Rolf Renne Ho Lam Chan Lluis Morey Daria Salyakina Martin Abba Sion Williams Joshua M Hare Pascal J Goldschmidt-Clermont Enrique A Mesri |
| author_facet | Julian Naipauer Santas Rosario Sachin Gupta Courtney Premer Omayra Méndez-Solís Mariana Schlesinger Virginia Ponzinibbio Vaibhav Jain Lauren Gay Rolf Renne Ho Lam Chan Lluis Morey Daria Salyakina Martin Abba Sion Williams Joshua M Hare Pascal J Goldschmidt-Clermont Enrique A Mesri |
| author_sort | Julian Naipauer |
| collection | DOAJ |
| 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. |
| format | Article |
| id | doaj-art-d419cd967ead4fd09bc2fbc2ad0223fd |
| institution | DOAJ |
| issn | 1553-7366 1553-7374 |
| language | English |
| publishDate | 2019-12-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Pathogens |
| spelling | doaj-art-d419cd967ead4fd09bc2fbc2ad0223fd2025-08-20T03:00:47ZengPublic Library of Science (PLoS)PLoS Pathogens1553-73661553-73742019-12-011512e100822110.1371/journal.ppat.1008221PDGFRA defines the mesenchymal stem cell Kaposi's sarcoma progenitors by enabling KSHV oncogenesis in an angiogenic environment.Julian NaipauerSantas RosarioSachin GuptaCourtney PremerOmayra Méndez-SolísMariana SchlesingerVirginia PonzinibbioVaibhav JainLauren GayRolf RenneHo Lam ChanLluis MoreyDaria SalyakinaMartin AbbaSion WilliamsJoshua M HarePascal J Goldschmidt-ClermontEnrique A MesriKaposi'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.https://journals.plos.org/plospathogens/article/file?id=10.1371/journal.ppat.1008221&type=printable |
| spellingShingle | Julian Naipauer Santas Rosario Sachin Gupta Courtney Premer Omayra Méndez-Solís Mariana Schlesinger Virginia Ponzinibbio Vaibhav Jain Lauren Gay Rolf Renne Ho Lam Chan Lluis Morey Daria Salyakina Martin Abba Sion Williams Joshua M Hare Pascal J Goldschmidt-Clermont Enrique A Mesri PDGFRA defines the mesenchymal stem cell Kaposi's sarcoma progenitors by enabling KSHV oncogenesis in an angiogenic environment. PLoS Pathogens |
| title | 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_short | 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 |
| url | https://journals.plos.org/plospathogens/article/file?id=10.1371/journal.ppat.1008221&type=printable |
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