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Effects of poor sleep on the immune cell landscape as assessed by single-cell analysis.

ABSTRACT: Poor sleep has become an important public health issue. With loss of sleep durations, poor sleep has been linked to the increased risks for diseases. Here we employed mass cytometry and single-cell RNA sequencing to obtain a comprehensive human immune cells landscape in the context of poor sleep, which was analyzed in the context of subset composition, gene signatures, enriched pathways, transcriptional regulatory networks, and intercellular interactions. Participants subjected to staying up had increased T and plasma cell frequency, along with upregulated autoimmune-related markers and pathways in CD4⁺ T and B cells. Additionally, staying up reduced the differentiation and immune activity of cytotoxic cells, indicative of a predisposition to infection and tumor development. Finally, staying up influenced myeloid subsets distribution and induced inflammation development and cellular senescence. These findings could potentially give high-dimensional and advanced insights for understanding the cellular and molecular mechanisms of pathologic conditions related to poor sleep.

SUBMITTER: Liu X

PROVIDER: S-EPMC8617259 | biostudies-literature | 2021 Nov

REPOSITORIES: biostudies-literature

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Effects of poor sleep on the immune cell landscape as assessed by single-cell analysis.

Liu Xiuxing X Chen Binyao B Huang Zhaohao Z Duan Runping R Li He H Xie Lihui L Wang Rong R Li Zhaohuai Z Gao Yuehan Y Zheng Yingfeng Y Zheng Yingfeng Y Su Wenru W

Communications biology 20211125 1

Poor sleep has become an important public health issue. With loss of sleep durations, poor sleep has been linked to the increased risks for diseases. Here we employed mass cytometry and single-cell RNA sequencing to obtain a comprehensive human immune cells landscape in the context of poor sleep, which was analyzed in the context of subset composition, gene signatures, enriched pathways, transcriptional regulatory networks, and intercellular interactions. Participants subjected to staying up had ...[more]

PMID: 34824394

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Project description:Purpose: We performed single-cell RNA sequencing (scRNA-seq), an unbiased and high-throughput single cell technology, to determine phenotype and function of peripheral immune cells in patients with diabetic macular edema (DME). Methods: Peripheral blood mononuclear cells (PBMCs) were isolated from DME patients and healthy controls (HC). The single-cell samples were loaded on the Chromium platform (10x Genomics) for sequencing. R package Seurat v3 was used for data normalizing, clustering, dimensionality reduction, differential expression analysis, and visualization. Results: We constructed a single-cell RNA atlas comprising 57,650 PBMCs (24,919 HC, 32,731 DME). We divided all immune cells into five major immune cell lineages, including monocytes (MC), T cells (TC), NK cells (NK), B cells (BC), and dendritic cells (DC). Our differential expression gene (DEG) analysis showed that MC was enriched of genes participating in the cytokine pathway and inflammation activation. We further subdivided MC into five subsets: resting CD14++ MC, proinflammatory CD14++ MC, intermediate MC, resting CD16++ MC and pro-inflammatory CD16++ MC. Remarkably, we revealed that the proinflammatory CD14++ monocytes predominated in promoting inflammation, mainly by increasingly production of inflammatory cytokines (TNF, IL1B, and NFKBIA) and chemokines (CCL3, CCL3L1, CCL4L2, CXCL2, and CXCL8). Gene Ontology (GO) and pathway analysis of the DEGs demonstrated that the proinflammatory CD14++ monocytes, especially in DME patients, upregulated inflammatory pathways including tumor necrosis factor-mediated signaling pathway, I-kappaB kinase/NF-kappaB signaling, and toll-like receptor signaling pathway. Conclusion: In this study, we construct the first immune landscape of DME patients with T2D and confirmed innate immune dysregulation in peripheral blood based on an unbiased scRNA-seq approach. And these results demonstrate potential target cell population for anti-inflammation treatments.

Dataset Information

Effects of poor sleep on the immune cell landscape as assessed by single-cell analysis.

Publications

Effects of poor sleep on the immune cell landscape as assessed by single-cell analysis.

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