Toward a more precise immunophenotypic and molecular definition of human cMoPs

ABSTRACT: Monocytes arise from haematopoietic progenitors in the bone marrow and play crucial roles in both homeostasis and inflammation. 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. ATAC-seq analysis of CD115⁺CD64hi/int cMoPs identified IRF8, PU.1, and also C/EBPδ as transcription factors putatively involved in monocyte development. Based on a more accurate definition and analysis, our data demonstrates the molecular complexity of human cMoPs.

ORGANISM(S): Homo sapiens

PROVIDER: GSE303727 | GEO | 2026/08/18

REPOSITORIES: GEO