Single-cell sequencing of tumor-associated macrophages in a Drosophila model

• DOI: 10.3389/fimmu.2023.1243797
• Publication Date: 2023-09-19T18:00:28Z
• Authors: Dilan Khalili; Mubasher Mohammed; Martin Kunc; Martina Sindlerova; Johan Ankarklev; Ulrich Theopold
• Keywords: Tumor progression

Introduction Tumor-associated macrophages may act to either limit or promote tumor growth, yet the molecular basis for path is poorly characterized. Methods We use a larval Drosophila model that expresses dominant-active version of Ras-oncogene (Ras V12 ) study dysplastic growth during early progression. performed single-cell RNA-sequencing macrophage-like hemocytes characterize these cells in tumor- compared wild-type larvae. Hemocytes included manually extracted tumor-associated- and circulating cells. Results discussion identified five distinct hemocyte clusters. In addition Ras larvae, we where activation effector caspases was inhibited, mimicking an apoptosis-resistant setting. Circulating from both models differ qualitatively control cells—they display enrichment genes involved cell division, which confirmed using proliferation assays. Split analysis further reveals strongest caspase-deficient Similarly, depending on model, attach tumors activate different sets immune effectors—antimicrobial peptides dominate response against alone, while caspase inhibition induces shift toward members proteolytic cascades. Finally, provide evidence transcript transfer between possibly other tissues. Taken together, our data support usefulness at organismic level.