Bone Marrow-Derived Human MSC as Precursors of KS Initiation and Progression Through Endothelial Differentiation and Cytokine Induction After KSHV Infection in a Pro-Angiogenic Environment.

NAIPAUER, J.; LACUNZA, E.; ANUJ A; MONTANARI M; COSO, O. A.; ABBA MC; MESRI E

Conferencia; 18th International Conference on Malignancies in HIV/AIDS; 2022

Cumulative evidence shows the importance of bone marrow-derived human Mesenchymal Stem Cells (hMSC) in Kaposi’s sarcoma (KS) Herpesvirus (KSHV) induced tumorigenesis. However, the KS spindle-cell progenitor subpopulation identity, defining markers, and specifi host conditions of KSHV-driven oncogenesis upon de novo infection are not well defined yet.We carried out KSHV infection of primary hMSCs and then subjected them to MSC or KS-like pro-angiogenic culture conditions. Three days after infection or one month after the selection of infected cells, we performed whole and single-cell RNA sequencing analyses of the Differentially Expressed Genes (DEGs).We found that processes such as extracellular matrix, angiogenesis, cell differentiation, cytokine activity, and cell proliferation were significantly more overrepresented in cells infected and grown in the KS-like conditions than in MSC cell culture conditions. By single-cell RNA sequencing, we found that different cell populations express different amounts of host and viral oncogenes depending on the environmental conditions in which the cells are growing after infection, leading to a subpopulation of infected cells in a pro-angiogenic environment expressing both viral and host oncogenes.These highlight the importance of environmental conditions in KSHV reprogramming of hMSC towards endothelial differentiation and transformation and closer to KS gene expression profiles, reinforcing the notion of these cell subpopulations as plausible KS precursors.