[Identification of a human progenitor strictly committed to monocytic differentiation: a counterpart of mouse cMoPs]

Monocytes give rise to macrophages and dendritic cells (DCs) under steady-state and inflammatory conditions, thereby contributing to host defense and tissue pathology. Inflammation triggers the differentiation of tissue-infiltrating monocytes into monocyte-derived macrophages and DCs, which are associated with homeostatic host defense reactions and inflammatory diseases. In mice, monocytes are divided into classical Ly6c^hi- and non-classical Ly6c^lo-expressing subsets. Ly6c^lo monocytes are present only in the blood; however, Ly6c^hi monocytes are found in blood and other tissues (wherein they differentiate into macrophages and DCs). In this context, most Ly6c^lo monocytes are derived from Ly6c^hi monocytes. In humans, monocytes comprise major CD14⁺CD16^- and other CD14⁺CD16⁺ and CD14^loCD16⁺ monocytes. A monocyte lineage-restricted common monocyte progenitor (cMoP) was previously identified in mice; herein, we introduce human cMoP, which was identified as a CLEC12A^hiCD64^hi subpopulation of conventional granulocyte-monocyte progenitors (cGMPs) in umbilical cord blood and bone marrow. The human cMoP produced monocyte subsets without showing any potential of differentiating into myeloid or lymphoid cells ex vivo. Within the cGMP population, we also identified revised GMPs that completely lacked DC and lymphoid potential, which sequentially produced cMoPs, pre-monocytes, and monocytes. Collectively, our findings enhance the current understanding of human myeloid cell differentiation pathways.