Dataset Information

Single-cell RNA-seq reveals new types of human blood dendritic cells, monocytes, and progenitors.

ABSTRACT: Dendritic cells (DCs) and monocytes play a central role in pathogen sensing, phagocytosis, and antigen presentation and consist of multiple specialized subtypes. However, their identities and interrelationships are not fully understood. Using unbiased single-cell RNA sequencing (RNA-seq) of ~2400 cells, we identified six human DCs and four monocyte subtypes in human blood. Our study reveals a new DC subset that shares properties with plasmacytoid DCs (pDCs) but potently activates T cells, thus redefining pDCs; a new subdivision within the CD1C+ subset of DCs; the relationship between blastic plasmacytoid DC neoplasia cells and healthy DCs; and circulating progenitor of conventional DCs (cDCs). Our revised taxonomy will enable more accurate functional and developmental analyses as well as immune monitoring in health and disease.

SUBMITTER: Villani AC

PROVIDER: S-EPMC5775029 | biostudies-literature | 2017 Apr

REPOSITORIES: biostudies-literature

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Single-cell RNA-seq reveals new types of human blood dendritic cells, monocytes, and progenitors.

Villani Alexandra-Chloé AC Satija Rahul R Reynolds Gary G Sarkizova Siranush S Shekhar Karthik K Fletcher James J Griesbeck Morgane M Butler Andrew A Zheng Shiwei S Lazo Suzan S Jardine Laura L Dixon David D Stephenson Emily E Nilsson Emil E Grundberg Ida I McDonald David D Filby Andrew A Li Weibo W De Jager Philip L PL Rozenblatt-Rosen Orit O Lane Andrew A AA Haniffa Muzlifah M Regev Aviv A Hacohen Nir N

Science (New York, N.Y.) 20170401 6335

Dendritic cells (DCs) and monocytes play a central role in pathogen sensing, phagocytosis, and antigen presentation and consist of multiple specialized subtypes. However, their identities and interrelationships are not fully understood. Using unbiased single-cell RNA sequencing (RNA-seq) of ~2400 cells, we identified six human DCs and four monocyte subtypes in human blood. Our study reveals a new DC subset that shares properties with plasmacytoid DCs (pDCs) but potently activates T cells, thus r ...[more]

PMID: 28428369

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Project description:BackgroundEmerging evidence from mouse models is beginning to elucidate the brain's immune response to tau pathology, but little is known about the nature of this response in humans. In addition, it remains unclear to what extent tau pathology and the local inflammatory response within the brain influence the broader immune system.MethodsTo address these questions, we performed single-cell RNA sequencing (scRNA-seq) of peripheral blood mononuclear cells (PBMCs) from carriers of pathogenic variants in MAPT, the gene encoding tau (n = 8), and healthy non-carrier controls (n = 8). Primary findings from our scRNA-seq analyses were confirmed and extended via flow cytometry, droplet digital (dd)PCR, and secondary analyses of publicly available transcriptomics datasets.ResultsAnalysis of ~ 181,000 individual PBMC transcriptomes demonstrated striking differential expression in monocytes and natural killer (NK) cells in MAPT pathogenic variant carriers. In particular, we observed a marked reduction in the expression of CX3CR1-the gene encoding the fractalkine receptor that is known to modulate tau pathology in mouse models-in monocytes and NK cells. We also observed a significant reduction in the abundance of nonclassical monocytes and dysregulated expression of nonclassical monocyte marker genes, including FCGR3A. Finally, we identified reductions in TMEM176A and TMEM176B, genes thought to be involved in the inflammatory response in human microglia but with unclear function in peripheral monocytes. We confirmed the reduction in nonclassical monocytes by flow cytometry and the differential expression of select biologically relevant genes dysregulated in our scRNA-seq data using ddPCR.ConclusionsOur results suggest that human peripheral immune cell expression and abundance are modulated by tau-associated pathophysiologic changes. CX3CR1 and nonclassical monocytes in particular will be a focus of future work exploring the role of these peripheral signals in additional tau-associated neurodegenerative diseases.

Dataset Information

Single-cell RNA-seq reveals new types of human blood dendritic cells, monocytes, and progenitors.

Publications

Single-cell RNA-seq reveals new types of human blood dendritic cells, monocytes, and progenitors.

Similar Datasets

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