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‑γ, IL‑10, TGF‑β). 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‑γ anchored the chemokine‑rich, IFN‑responsive pole (Ccl7, Ccl2, Ccl12), whereas TGF‑β anchored a matrix‑remodeling/angiogenic pole (Mmp14, Cav1, Cspg4); IL‑10 shifted modestly toward the IFN‑low quadrant.