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

Frontiers in Immunology

Immunology

Dilan Khalili¹  Martina Sindlerova¹  Ulrich Theopold¹  Johan Ankarklev¹  Mubasher Mohammed¹  Martin Kunc² 

[1] The Wenner-Gren Institute, Department of Molecular Biosciences, Stockholm University, Stockholm, Sweden;The Wenner-Gren Institute, Department of Molecular Biosciences, Stockholm University, Stockholm, Sweden;Department of Clinical Medicine, Aarhus University, Aarhus, Denmark;

关键词: Drosophila melanogaster;    macrophages;    tumor model;    hemocyte;    single-cell transcriptomics;    ScRNA-seq;   

DOI  :  10.3389/fimmu.2023.1243797

 received in 2023-06-21, accepted in 2023-08-31,  发布年份 2023

来源: Frontiers

【 摘 要 】

IntroductionTumor-associated macrophages may act to either limit or promote tumor growth, yet the molecular basis for either path is poorly characterized.MethodsWe use a larval Drosophila model that expresses a dominant-active version of the Ras-oncogene (RasV12) to study dysplastic growth during early tumor progression. We performed single-cell RNA-sequencing of macrophage-like hemocytes to characterize these cells in tumor- compared to wild-type larvae. Hemocytes included manually extracted tumor-associated- and circulating cells.Results and discussionWe identified five distinct hemocyte clusters. In addition to RasV12 larvae, we included a tumor model where the activation of effector caspases was inhibited, mimicking an apoptosis-resistant setting. Circulating hemocytes from both tumor models differ qualitatively from control wild-type cells—they display an enrichment for genes involved in cell division, which was confirmed using proliferation assays. Split analysis of the tumor models further reveals that proliferation is strongest in the caspase-deficient setting. Similarly, depending on the tumor model, hemocytes that attach to tumors activate different sets of immune effectors—antimicrobial peptides dominate the response against the tumor alone, while caspase inhibition induces a shift toward members of proteolytic cascades. Finally, we provide evidence for transcript transfer between hemocytes and possibly other tissues. Taken together, our data support the usefulness of Drosophila to study the response against tumors at the organismic level.

【 授权许可】

Unknown   
Copyright © 2023 Khalili, Mohammed, Kunc, Sindlerova, Ankarklev and Theopold