Description

Discovery of Human Immune Cell Populations by Single Cell Profiling

Alexandra-Chloé Villani

Broad Institute of MIT and Harvard, Cambridge, MA, USA

Achieving detailed understanding of the composition and function of the human immune system at the fundamental unit of life — the cell — is essential to determining the prerequisites of health and disease. Historically, leukocyte populations have been defined by a combination of morphology, localization, functions, developmental origins, and the expression of a restricted set of markers. However, these strategies are inherently biased and are recognized today as inadequate. Single-cell genomics analyses now provide an unbiased, data-driven way of systematically detecting cellular states and subtypes, and can reveal diverse simultaneous facets of cellular identity, from discrete cell types to continuous dynamic transitions, that cannot be defined by a handful of pre-defined markers or for which markers are not yet known. We combined single cell ‘omics’ strategies together with in-depth follow-up profiling, phenotypic characterization, and functional studies of prospectively isolated human immune cell subsets, as defined by single-cell RNA sequencing data, to overcome such limitations. Our analyses revealed the detailed biological landscape of human blood myeloid populations, enabling the discovery, re-classification, and characterization of several novel cell subsets of dendritic cells, monocytes, and progenitors in health and disease.This strategy reopens the definition of cell type, allowing for a more sophisticated and complete view of a cell.Our revised myeloid cell taxonomy will enable more accurate functional and developmental analyses as well as immune monitoring in health and disease. This approach also forms a basis for constructing a comprehensive human cell atlas.