Single-cell Transcriptome Mapping Identifies Common and Cell-type Specific Genes Affected by Acute Delta9-tetrahydrocannabinol in Humans
Single-cell Transcriptome Mapping Identifies Common and Cell-type Specific Genes Affected by Acute Delta9-tetrahydrocannabinol in Humans
Abstract Delta 9-tetrahydrocannabinol (THC), the principal psychoactive constituent of cannabis, is also known to modulate immune response in peripheral 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 administration of THC acutely alters gene expression in 15,973 human blood immune cells. Controlled for high inter-individual transcriptomic variability, we identified 294 transcriptome-wide significant genes among eight cell types including 69 common genes and 225 cell-type specific genes affected by acute THC administration, including those genes involving not only in immune response, cytokine production, but signal transduction, and 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. We found that THC alters the correlation of cannabinoid receptor gene, CNR2, with other genes in B cells, in which CNR2 showed the highest level of expression. This comprehensive cell-specific transcriptomic profiling identified novel genes regulated by THC and provides important insights into THC’s acute effects on immune function that may have important medical implications.
Shu Chang、Liang Xiaoyu、Zhang Xinyu、Aouizerat Bradley E、D?ˉSouza Deepak C.、Xu Ke、Hu Ying、Ganesh Suhas、Yan Chunhua、Krystal John H、Ranganathan Mohini
Department of Psychiatry, Yale School of Medicine||Connecticut Veteran Healthcare SystemDepartment of Psychiatry, Yale School of Medicine||Connecticut Veteran Healthcare SystemDepartment of Psychiatry, Yale School of Medicine||Connecticut Veteran Healthcare SystemBluestone Center for Clinical Research, College of Dentistry, New York University||Department of Oral and Maxillofacial Surgery, College of Dentistry, New York UniversityDepartment of Psychiatry, Yale School of Medicine||Connecticut Veteran Healthcare SystemDepartment of Psychiatry, Yale School of Medicine||Connecticut Veteran Healthcare SystemCenter for Biomedical Information and Information Technology, National Cancer InstituteDepartment of Psychiatry, Yale School of Medicine||Connecticut Veteran Healthcare SystemCenter for Biomedical Information and Information Technology, National Cancer InstituteDepartment of Psychiatry, Yale School of Medicine||Connecticut Veteran Healthcare SystemDepartment of Psychiatry, Yale School of Medicine||Connecticut Veteran Healthcare System
基础医学细胞生物学分子生物学
Delta-9-tetrahydrocannabinolsingle cell transcriptomeperipheral blood mononuclear cellsdifferential gene expressiongene set enrichment analysisgene co-expression
Shu Chang,Liang Xiaoyu,Zhang Xinyu,Aouizerat Bradley E,D?ˉSouza Deepak C.,Xu Ke,Hu Ying,Ganesh Suhas,Yan Chunhua,Krystal John H,Ranganathan Mohini.Single-cell Transcriptome Mapping Identifies Common and Cell-type Specific Genes Affected by Acute Delta9-tetrahydrocannabinol in Humans[EB/OL].(2025-03-28)[2025-07-21].https://www.biorxiv.org/content/10.1101/638254.点此复制
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