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

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...

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Published inScientific 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
LanguageEnglish
Published London Nature Publishing Group UK 26.02.2020
Nature Publishing Group
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ISSN2045-2322
2045-2322
DOI10.1038/s41598-020-59827-1

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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.
AbstractList 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.
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.
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.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.
ArticleNumber 3450
Author Liang, Xiaoyu
Osafo-Addo, Awo
Zhang, Xinyu
Ranganathan, Mohini
Yan, Chunhua
Xu, Ke
Hu, Ying
Shu, Chang
Krystal, John H.
D’Souza, Deepak C.
Aouizerat, Bradley E.
Ganesh, Suhas
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Snippet 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...
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...
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...
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...
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Publisher
StartPage 3450
SubjectTerms 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
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Title Single-cell Transcriptome Mapping Identifies Common and Cell-type Specific Genes Affected by Acute Delta9-tetrahydrocannabinol in Humans
URI https://link.springer.com/article/10.1038/s41598-020-59827-1
https://www.ncbi.nlm.nih.gov/pubmed/32103029
https://www.proquest.com/docview/2365159017
https://www.proquest.com/docview/2366647451
https://pubmed.ncbi.nlm.nih.gov/PMC7044203
https://www.nature.com/articles/s41598-020-59827-1.pdf
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