We identified 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, inflammation and wound healing are critical for KSHV sarcomagenesis. Here, PDGFRA is linked to Kaposi's sarcoma.