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Single-cell analysis reveals dynamic changes of A549 cells in monolayer, A549 xenografts in nude mice, and xenografts after exposure to dacomitinib

ABSTRACT: The in vitro A549 cells, and A549 xenografts in nude mouse were two classic and commonly used models for anti-cancer drug discovery. Here dynamic changes of the A549 models, and also A549 xenografts after exposure to dacomitinib were revealed by single-cell transcriptome analysis.

ORGANISM(S): Mus musculus Homo sapiens

PROVIDER: GSE220435 | GEO | 2023/12/01

REPOSITORIES: GEO

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Project description:The pathophysiology of endometriotic lesion development remains unclear but involves a complex interaction between ectopic endometrium and host peritoneal tissues. We hypothesised that disruption of this interaction was likely to suppress endometriotic lesion formation. We hoped to delineate the molecular and cellular dialogue between ectopic human endometrium and peritoneal tissues in nude mice, as a first step towards testing this hypothesis. Human endometrium was xenografted into nude mice and the resulting lesions were analysed using microarrays. A novel technique was developed that unambiguously determined whether RNA transcripts identified by the microarray analyses originated from human cells (endometrium) or mouse cells (stroma). Four key pathways (ubiquitin/proteosome, inflammation, tissue remodelling/repair and ras-mediated oncogenesis) were revealed, that demonstrated communication between host stromal cells and ectopic endometrium. Morphometric analysis of nude mouse lesions confirmed that necrosis, inflammation, healing and repair and cell proliferation occurred during xenograft development. These processes were entirely consistent with the molecular networks revealed by the microarray data. The transcripts detected in the xenografts overlapped with transcripts differentially expressed in a comparison between paired eutopic and ectopic endometrium from human endometriotic patients. For the first time components of the interaction between ectopic endometrium and peritoneal stromal tissues have been revealed in ectopic endometrial lesions. Targeted disruption of this dialogue is likely to disrupt endometriotic tissue formation and may prove to be an effective therapeutic strategy for endometriosis. Experiment Overall Design: Xenografts of human endometrium in nude mice hybridised to both human and mouse specific genechips. 2 biological replicates, at 3 time points. Control human endometrium and mouse pertioneum were hybridised to both human and mouse genechips

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Single-cell analysis reveals dynamic changes of A549 cells in monolayer, A549 xenografts in nude mice, and xenografts after exposure to dacomitinib

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