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Published on: March 5, 2022
A single-nucleus multiome analysis of transcriptome and chromatin accessibility reveals cell-type-specific immune
Mingrui Li1,2,3, Kesava Asam4,5, Xiaoke Duan1,3
1Department of Psychiatry, Yale School of Medicine, New Haven, CT, U.S.A.
Insights
Cannabis use significantly impacts immune cells in people with HIV (PWH). Chronic exposure alters gene expression and epigenetic regulation in immune cells, affecting inflammation and cell communication.
Area of Science:
- Immunology
- Epigenetics
- HIV Research
Background:
- Cannabis use is increasing among people with HIV (PWH).
- Understanding cannabis's effects on immune function in PWH is crucial.
- Previous research has not fully elucidated the molecular mechanisms.
Purpose of the Study:
- To investigate how chronic cannabis exposure affects immune cell gene expression and chromatin accessibility in PWH.
- To identify specific molecular pathways and regulators involved in cannabis-induced immunomodulation.
- To characterize cell-type-specific responses to cannabis in PWH.
Main Methods:
- Single-nucleus multi-omic profiling of peripheral blood mononuclear cells (PBMCs).
- Analysis of gene expression (DEGs) and chromatin accessibility.
- Identification of transcription factor regulators and cell-cell communication networks.
Main Results:
- Numerous cell-type-specific differentially expressed genes (DEGs) were identified between cannabis users and non-users.
- Cannabis use altered pro- and anti-inflammatory gene expression in a cell-dependent manner.
- Epigenetic changes, including differential chromatin accessibility, correlated with DEGs, implicating transcription factors like NFKB1 and FOS.
- Cannabis exposure modulated communication between monocytes and lymphocytes.
Conclusions:
- Cannabis induces profound, complex, and dynamic immunomodulatory effects in PWH.
- Transcriptional changes in immune cells are regulated, in part, by epigenetic mechanisms.
- These findings highlight the intricate interplay between cannabis, immune function, and epigenetic regulation in PWH.
Abstract:
As cannabis use continues to rise among people with HIV (PWH), understanding its impact on immune function in this population is becoming increasingly important. To provide new insights on how cannabis modulates immune function, we analyzed single-nucleus multi-omic profiles of peripheral blood mononuclear cells (PBMCs) from PWH to characterize the changes in gene expression and chromatin accessibility associated with chronic cannabis exposure. We identified numerous differentially expressed genes (DEGs) between cannabis users and non-users in each cell type, approximately half of which were unique to individual cell types. Changes in pro- and anti-inflammatory gene expression associated with cannabis use are dependent on cell lineage and type. We identified hundreds of differential chromatin accessibility regions in each cell type, including cis-regulatory elements correlated with cell-type-dependent DEGs (e.g. NFKBIA in CD4+ T cells and CCL3L1 in classical monocytes). Multiple cannabis-associated transcription factors (e.g., NFKB1, FOS, and TCF7) emerge as regulators of the differentially expressed inflammatory genes. Furthermore, cannabis altered the communication between classical monocytes and lymphocytes. These findings indicate that cannabis-induced immunomodulatory effects are profound, dynamic and complex among cell types and that transcriptional changes are regulated at least in part by epigenetic mechanisms.
