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

Alexandra-Chloé Villani; Rahul Satija; Gary Reynolds; Siranush Sarkizova; Karthik Shekhar; James Fletcher; Morgane Griesbeck; Andrew Butler; Shiwei Zheng; Suzan Lazo; Laura Jardine; David Dixon; Emily Stephenson; Emil Nilsson; Ida Grundberg; David McDonald; Andrew Filby; Weibo Li; Philip L De Jager; Orit Rozenblatt-Rosen; Andrew A Lane; Muzlifah Haniffa; Aviv Regev; Nir Hacohen

doi:10.1126/science.aah4573

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

Science. 2017 Apr 21;356(6335):eaah4573. doi: 10.1126/science.aah4573.

Authors

Alexandra-Chloé Villani^{1

2}, Rahul Satija^{3

4

5}, Gary Reynolds⁶, Siranush Sarkizova³, Karthik Shekhar³, James Fletcher⁶, Morgane Griesbeck⁷, Andrew Butler^{4

5}, Shiwei Zheng^{4

5}, Suzan Lazo⁸, Laura Jardine⁶, David Dixon⁶, Emily Stephenson⁶, Emil Nilsson⁹, Ida Grundberg⁹, David McDonald⁶, Andrew Filby⁶, Weibo Li^{3

2}, Philip L De Jager^{3

10}, Orit Rozenblatt-Rosen³, Andrew A Lane^{3

8}, Muzlifah Haniffa^{11

12}, Aviv Regev^{1

13

14}, Nir Hacohen^{1

2}

Affiliations

¹ Broad Institute of MIT and Harvard, Cambridge, MA, USA. cvillani@broadinstitute.org m.a.haniffa@newcastle.ac.uk aregev@broadinstitute.org nhacohen@mgh.harvard.edu.
² Center for Cancer Research, Massachusetts General Hospital, Department of Medicine, Boston, MA, USA.
³ Broad Institute of MIT and Harvard, Cambridge, MA, USA.
⁴ New York Genome Center, New York University Center for Genomics and Systems Biology, New York, NY, USA.
⁵ New York University Center for Genomics and Systems Biology, New York, NY, USA.
⁶ Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, UK.
⁷ Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology, and Harvard University, Cambridge, MA, USA.
⁸ Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
⁹ Olink Proteomics, Watertown, MA, USA.
¹⁰ Program in Translational NeuroPsychiatric Genomics, Department of Neurology, Brigham and Women's Hospital and Harvard Medical School.
¹¹ Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, UK. cvillani@broadinstitute.org m.a.haniffa@newcastle.ac.uk aregev@broadinstitute.org nhacohen@mgh.harvard.edu.
¹² Department of Dermatology, Royal Victoria Infirmary, Newcastle Hospitals NHS Foundation Trust, UK.
¹³ Department of Biology and Koch Institute, Massachusetts Institute of Technology, Cambridge, MA, USA.
¹⁴ Howard Hughes Medical Institute, Chevy Chase, MD, USA.

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.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Adult
Antigen Presentation
Classification
Dendritic Cells / classification*
Dendritic Cells / immunology
Female
Gene Expression Profiling
Humans
Lymphocyte Activation
Male
Monitoring, Immunologic
Monocytes / classification*
Monocytes / immunology
Neoplasms / immunology
Neoplasms / pathology
Sequence Analysis, RNA
Single-Cell Analysis
T-Lymphocytes / immunology*
Transcriptome
Young Adult

Abstract

Publication types

MeSH terms

Grants and funding