Toward a more precise immunophenotypic and molecular definition of human cMoPs

Human common monocyte progenitors (cMoPs) were originally identified as CLEC12A⁺CD64hi cells but have recently been redefined as CD115⁺CD64hi/int cells. We therefore evaluated whether CLEC12A⁺CD64hi cMoPs and CD115⁺CD64hi/int cMoPs represent the same cell type using flow cytometry, scRNA-seq, morphological, and functional analyses.

We demonstrate that including CD115 in the gating strategy, rather than CLEC12A, yields a more accurate definition of cMoPs. Differentiation assays demonstrate the transition of CD115⁺CD64int cMoPs into CD115⁺CD64hi cMoPs and a comparable capacity for the two cMoPs to generate monocyte progeny. scRNA-seq clustering of the CD115⁺CD64hi/int cMoPs identified five different transcriptional features, including maturation-associated programs, IFN response and stress-related genes.