Behind the monocyte’s mystique: uncovering their developmental trajectories and fates

Abstract

Monocytes are circulating myeloid cells that are derived from dedicated progenitors in the bone marrow. Originally thought of as mere precursors for the replacement of tissue macrophages, it is increasingly clear that monocytes execute distinct effector functions and may give rise to monocyte-derived cells with unique properties from tissue resident macrophages. Recently, the advent of novel experimental approaches such as single cell analysis and fate mapping tools has uncovered an astonishing display of monocyte plasticity and heterogeneity, which we believe has emerged as a key theme in the field of monocyte biology in the last decade. Monocyte heterogeneity is now recognized to develop as early as the progenitor stage through specific imprinting mechanisms, giving rise to specialized effector cells in the tissue. At the same time, monocytes must overcome their susceptibility towards cellular death to persist as monocyte-derived cells in the tissues. Environmental signals that preserve their heterogenic phenotypes and govern their eventual fates remain incompletely understood. In this review, we will summarize recent advances on the developmental trajectory of monocytes and discuss emerging concepts that contributes to the burgeoning field of monocyte plasticity and heterogeneity.

Ly6Chi Monocytes Are Metabolically Reprogrammed in the Blood during Inflammatory Stimulation and Require Intact OxPhos for Chemotaxis and Monocyte to Macrophage Differentiation

“…Conventional cell surface expression identifies our input cells as a homogenous population; therefore, it is striking that we can identify significant heterogeneity within the cells present not only between the four experimental groups but within each experimental group. It is now widely accepted that analysis of cell surface markers vastly underestimates the heterogeneity within monocyte populations and that while cell surface expression may remain the same under inflammatory conditions, the transcriptome of individual cells may change rapidly to meet the changing demands of the cell [ 46 , 47 ]. Our data are consistent with a model of heightened heterogeneity within classically defined immune cell populations, and that transcriptomes may diverge before classical cell surface markers do.…”