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| Status |
Public on Dec 12, 2019 |
| Title |
PDGFRA Defines the Mesenchymal Stem Cell Kaposi’s Sarcoma Progenitors by Enabling KSHV Oncogenesis in an Angiogenic Environment [RNA-seq] |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
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.
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| Overall design |
We designed a novel model of “de novo” KSHV oncogenesis based on infection of PDGFRA-positive mesenchymal stem cell progenitors cultured in pro-angiogenic/vasculogenic KS-like growth conditions. This system serves as a unique and robust platform to identify KSHV oncogenic-pathways and their relationship with cellular lineages and extracellular growth environments. Additionally, it can further be exploited to genetically dissect and elucidate viral, host-cell and environmental features of KS pathobiology.
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| Contributor(s) |
Mesri EA, Naipauer J, Abba MC |
| Citation(s) |
31881074 |
| |
| Submission date |
Dec 11, 2019 |
| Last update date |
Feb 18, 2020 |
| Contact name |
Martin Carlos Abba |
| E-mail(s) |
mcabba@gmail.com
|
| Phone |
054-221-4236711
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| Organization name |
School of Medical Sciences - UNLP
|
| Lab |
CINIBA
|
| Street address |
60 y 120
|
| City |
La Plata |
| State/province |
Buenos Aires |
| ZIP/Postal code |
1900 |
| Country |
Argentina |
| |
|
| Platforms (1) |
| GPL19057 |
Illumina NextSeq 500 (Mus musculus) |
|
| Samples (14)
|
| GSM4215171 |
KSHV positive Pα(+)S MSCs in KS media 1 |
| GSM4215172 |
KSHV positive Pα(+)S MSCs in KS media 2 |
| GSM4215173 |
KSHV positive Pα(+)S MSCs in KS media 3 |
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| This SubSeries is part of SuperSeries: |
| GSE141868 |
PDGFRA Defines the Mesenchymal Stem Cell Kaposi’s Sarcoma Progenitors by Enabling KSHV Oncogenesis in an Angiogenic Environment |
|
| Relations |
| BioProject |
PRJNA594986 |
| SRA |
SRP237268 |
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