Cytokine–ontogeny interaction shapes macrophage transcriptional states (M-CSF–derived macrophages)

In M-CSF–derived macrophages, bulk RNA-seq was performed on five biological replicates per cytokine condition (IL-4, IFN-?, IL-10, TGF-ß). IL-4 dominated PC1 (54% variance) driving a reparative module with EMT, UPR, and mTORC1 signatures, while IFN-stimulated genes (Gbp4, Ifi44) were repressed. PC2 (26% variance) spanned an inflammatory-to-remodeling continuum: IFN-? anchored the chemokine-rich, IFN-responsive pole (Ccl7, Ccl2, Ccl12), whereas TGF-ß anchored a matrix-remodeling/angiogenic pole (Mmp14, Cav1, Cspg4); IL-10 shifted modestly toward the IFN-low quadrant. Overall design: M-CSF–derived macrophages were stimulated with IL-4, IFN-?, IL-10, TGF-ß, or left untreated (control). Bulk RNA-seq was performed on five biological replicates per condition.