Macrophages derived from human induced pluripotent stem cells (iPSCs) serve as a high-fidelity cellular model for investigating HIV-1, dengue, and influenza viruses
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ABSTRACT: Macrophages are important target cells for diverse viruses, and thus represent a valuable model system for studying virus biology. Isolation of primary human macrophages is done by culture of dissociated tissues or from differentiated blood monocytes, but these methods are both time consuming and result in low numbers of recovered macrophages. Here, we explore whether macrophages derived from human induced pluripotent stem cells (iPSCs)—which proliferate indefinitely and potentially provide unlimited starting material— could serve as a faithful model system for studying virus biology. Human iPSC-derived monocytes were differentiated into macrophages and then infected with HIV-1, dengue virus, or influenza virus as model macrophage-tropic human viruses. We show that iPSC-derived macrophages supported the replication of these viruses with similar kinetics and phenotypes to human blood monocyte-derived macrophages. These iPSC-derived macrophages were virtually indistinguishable from human blood monocyte-derived macrophages based on surface marker expression analysis (flow cytometry), transcriptomics (RNA-seq), and chromatin accessibility profiling (ATAC-seq) approaches. iPSC lines were additionally generated from nonhuman primate (chimpanzee) fibroblasts. When challenged with dengue virus, human and nonhuman primate iPSC-derived macrophages show differential susceptibility to infection, thus providing a valuable resource for studying the species-tropism of viruses. Collectively, our results substantiate iPSC-derived macrophages as an alternative to blood monocyte-derived macrophages for the study of virus biology.
ORGANISM(S): Homo sapiens
PROVIDER: GSE252979 | GEO | 2024/01/14
REPOSITORIES: GEO
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