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Longitudinal proteomic module configurations differ across human monocyte-derived differentiation and polarization conditions

Navarro Quiroz, R.; Escorcia Lindo, K.; Jaruffe Pinilla, A.; Luna-Rodriguez, I. K.; Diaz-Olmos, Y.; Geribaldi-Doldan, N.; Fernandez-Ponce, C.; Zarate Penate, E.; Bello Lemus, Y.; Pacheco Lugo, L.; Pacheco Londono, L.; Acosta-Hoyos, A.; Navarro Quiroz, E.

2026-06-26 immunology
10.64898/2026.06.24.734366 bioRxiv
Show abstract

Monocytes are key innate immune cells capable of differentiating into macrophages and dendritic cells, or adopting distinct polarization states in response to microenvironmental signals. Despite advances in transcriptomics, the proteomic landscape underlying these differentiation and polarization trajectories remains incompletely characterized. Here, we performed a longitudinal proteomic analysis of human monocyte-derived macrophages and dendritic cells under multiple polarization conditions using publicly available mass spectrometry datasets. We applied weighted protein co-expression network analysis (WPCNA) to identify proteomic modules and characterized their temporal dynamics across differentiation and polarization conditions. Our results reveal that proteomic module configurations are condition-specific and exhibit distinct longitudinal trajectories, with modules enriched in immune signaling, metabolic reprogramming, and cytoskeletal remodeling pathways. Hub proteins within these modules represent potential regulatory nodes governing monocyte fate decisions. These findings provide a systems-level view of monocyte proteome organization and highlight the divergent molecular programs that underlie functional specialization during differentiation and polarization.

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