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

• Published in: Scientific reports Vol. 10; no. 1; p. 3450
• Main Authors: Hu, Ying, Ranganathan, Mohini, Shu, Chang, Liang, Xiaoyu, Ganesh, Suhas, Osafo-Addo, Awo, Yan, Chunhua, Zhang, Xinyu, Aouizerat, Bradley E., Krystal, John H., D’Souza, Deepak C., Xu, Ke
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 26.02.2020; Nature Publishing Group
• Subjects: 38/39; 631/208; 631/208/199; 692/4017; Acute effects; Apoptosis; Apoptosis - drug effects; B-Lymphocytes - cytology; B-Lymphocytes - drug effects; B-Lymphocytes - metabolism; Blood cells; CD8-Positive T-Lymphocytes - cytology; CD8-Positive T-Lymphocytes - metabolism; Cell proliferation; Cell Proliferation - drug effects; Cluster Analysis; Cytokines - metabolism; Dronabinol - analogs & derivatives; Dronabinol - pharmacology; Gene expression; Gene Expression Profiling - methods; Gene Expression Regulation - drug effects; Gene mapping; Gene Regulatory Networks - drug effects; Gene set enrichment analysis; Humanities and Social Sciences; Humans; Immune response; Immunity, Active - drug effects; Leukocytes, Mononuclear - cytology; Leukocytes, Mononuclear - drug effects; Leukocytes, Mononuclear - metabolism; Male; multidisciplinary; Peripheral blood; Receptor, Cannabinoid, CB2 - genetics; Receptor, Cannabinoid, CB2 - metabolism; Science; Science (multidisciplinary); Single-Cell Analysis; Tetrahydrocannabinol; Toxicity; Young Adult
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-020-59827-1

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.