Figure 1.

Pathways of myeloid cell differentiation. In the steady-state, distinct mouse monocyte subsets arise independently from common myeloid progenitors (CMPs; LKS⁻ CD34⁺ FcγR^lo Flt3⁺ CD115^lo cells) via granulocyte-monocyte progenitors (GMPs; LKS⁻ CD34⁺ FcγR^hi Ly6C⁻) and monocyte-DC progenitors (MDPs; LKS⁻ CD34⁺ FcγR^lo Flt3⁺ CD115^hi). GMPs also produce neutrophils (via granulocyte progenitors, GPs), and MDPs yield cDCs and pDCs (via common DC progenitors, CDPs). Functionally distinct subsets of classical monocytes (Ly6C^hi in mice) are produced by both GMPs and MDPs. Non-classical (Ly6C⁻) monocytes and macrophages, also arise via both pathways and may exhibit functional differences. In contrast, monocyte-derived DCs (moDCs, which are ontogenetically and functionally distinct from cDCs and pDCs) arise exclusively from MDP-derived monocytes, and GMPs produce a neutrophil-like subset of classical monocytes. Monocyte-committed progenitors arising from GMPs (known as MPs) and MDPs (known as cMoPs) are both found in the LKS⁻ CD34⁺ FcγR^hi Ly6C⁺ CD115^hi fraction of mouse bone marrow; it is not currently possible to separate them using surface markers, but MPs and cMoPs are revealed as distinct cell clusters by single-cell RNA sequencing.