Single-cell Transcriptome Mapping Identifies Common and Cell-type Specific Genes Affected by Acute...

Area of Science:

• Immunology
• Genomics
• Pharmacology

Background:

• Delta-9-tetrahydrocannabinol (THC) is recognized for modulating peripheral blood cell immune responses.
• The precise mechanisms underlying THC's influence on human immune cell gene expression are not well understood.

Purpose of the Study:

• To investigate the acute effects of THC on gene expression in human immune cells at a single-cell level.
• To identify common and cell-type-specific genes regulated by THC in the immune system.

Main Methods:

• Employed a within-subject design coupled with single-cell transcriptome mapping.
• Analyzed gene expression changes in 15,973 individual blood cells following THC administration.
• Utilized gene set enrichment analysis to interpret functional impacts.

Main Results:

• Identified 294 transcriptome-wide significant genes affected by acute THC exposure across eight immune cell types.
• Discovered 69 common genes and 225 cell-type-specific genes impacted by THC, involving immune response, cytokine production, proliferation, and apoptosis.
• Revealed THC-induced perturbations in cell-type-specific intracellular gene expression correlations within distinct transcriptomic sub-clusters.

Conclusions:

• Comprehensive single-cell transcriptomic profiling elucidates THC's acute effects on immune cell gene expression.
• Findings highlight both shared and unique molecular responses to THC across different immune cell populations.
• These insights into THC's immunomodulatory actions may hold significant medical implications.