DESCRIPTION:
Translational rhesus macaque model of voluntary ethanol self-administration that closely recapitulates human drinking patterns and chronicity. In this study, we examined the effects of chronic heavy drinking (CHD) on blood monocytes in control and CHD female macaques after 12 months of daily ethanol consumption. In depth scRNA-Seq analysis of purified monocytes revealed significant shifts in classical monocyte subsets with accumulation of cells expressing markers of hypoxia (HIF1A) and inflammation (NFkB signaling pathway) in CHD macaques. The increased presence of monocyte subsets skewed towards inflammatory phenotypes was complemented by epigenetic analysis, which revealed higher accessibility of promoter regions that regulate genes involved in cytokine signaling pathways. Sequencing reads were aligned to the Mmul_8.0.1 reference genome using cellranger v3.1 (52) (10X Genomics). Quality control steps were performed prior to downstream analysis with Seurat, filtering out cells with fewer than 200 unique features and cells with greater than 20% mitochondrial content. Control and CHD datasets were down sampled to 4680 cells each and integrated in Seurat (53) using the IntegrateData function. Data normalization and variance stabilization were performed, correcting for differential effects of mitochondrial and cell cycle gene expression levels. Clustering was performed using the first 20 principal components. Small clusters with an over-representation of B and T cell gene expression were removed for downstream analysis. Clusters were visualized using uniform manifold approximation and projection (UMAP) and further characterized into distinct monocyte subsets using the FindMarkers function (Supplementary Table 3). p_val_adj < 0.05, avg_log_fc > 0.25.
LABEL:
Macaque blood monocyte scRNA cluster 6 CHD and control (non-classical)_qvalue
SCORE TYPE:
Q-Value
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