Proteomic screening identifies a block in neutrophil differentiation starting at the preneutrophil stage in G-CSFR-deficient Dmp1Cre.Socs3^f/f mice. (A) Schematic of experiment. (B-C) Principal component analysis (B) and gene set enrichment analysis (C) of Dmp1Cre.Socs3^f/f and Dmp1Cre.Socs3^f/f.Csf3r^–/– marrow proteomes, showing clear separation, and strong downregulation of neutrophil degranulation pathway proteins and Rho GTPases, with upregulation of mitochondrial transport, ETC and TCA cycle proteins. (D-E) UMAP (D) and heat map (E) showing transcript abundance of all proteins significantly downregulated (log2 [fold change] of >0.5) in Dmp1Cre.Socs3^f/f.Csf3r^–/– compared with Dmp1Cre.Socs3^f/f marrow aligned with the cell subtypes present in endosteal bone and marrow compartments of wild-type mice by single-cell RNA-seq. UMAP scale bar on right indicates enrichment score of all neutrophil-related transcripts within each cell type. Heat map indicates abundance of each transcript in the indicated cell type relative to the average transcript level across all cell clusters. ETC, electron transport chain; LC-MS/MS, liquid chromatography-tandem mass spectrometry; TCA, tricarboxylic acid; UMAP, uniform manifold approximation and projection.