Single-cell Transcriptome Mapping Identifies Common and Cell-type Specific Genes Affected by Acute Delta9-tetrahydrocannabinol in Humans

单细胞转录组图谱鉴定出受急性 Delta9-四氢大麻酚影响的人类常见基因和细胞类型特异性基因

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作者:Ying Hu, Mohini Ranganathan, Chang Shu, Xiaoyu Liang, Suhas Ganesh, Awo Osafo-Addo, Chunhua Yan, Xinyu Zhang, Bradley E Aouizerat, John H Krystal, Deepak C D'Souza, Ke Xu

Abstract

Delta-9-tetrahydrocannabinol (THC) is known to modulate immune response in peripheral blood cells. The mechanisms of THC's effects on gene expression in human immune cells remains poorly understood. Combining a within-subject design with single cell transcriptome mapping, we report that THC acutely alters gene expression in 15,973 blood cells. We identified 294 transcriptome-wide significant genes among eight cell types including 69 common genes and 225 cell-type-specific genes affected by THC administration, including those genes involving in immune response, cytokine production, cell proliferation and apoptosis. We revealed distinct transcriptomic sub-clusters affected by THC in major immune cell types where THC perturbed cell-type-specific intracellular gene expression correlations. Gene set enrichment analysis further supports the findings of THC's common and cell-type-specific effects on immune response and cell toxicity. This comprehensive single-cell transcriptomic profiling provides important insights into THC's acute effects on immune function that may have important medical implications.

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