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These two populations differ in developmental origin: AMs mainly derive from fetal liver progenitors, whereas IMs originate from yolk sac progenitors and can be further supplemented by recruited blood monocytes ( The dynamic changes and phenotypic characteristics of these macrophage populations have been validated through single-cell RNA sequencing and flow cytometry ( 3 Macrophage polarization Macrophages, as a functionally diverse class of immune cells, exhibit high plasticity and can adapt to different tissue microenvironments to perform a wide range of functions ( 3.1 M1 macrophages M1 macrophages are primarily induced by signals such as bacterial lipopolysaccharide (LPS) and interferon- (IFN-), which activate transcriptional pathways including signal transducer and activator of transcription 1(STAT1) and NF-B to initiate and sustain a robust pro-inflammatory response ( 3.2 M2 macrophages M2 macrophages are mainly polarized under the mediation of IL-4, IL-13, and IL-10 through activation of the STAT6 signaling pathway ( M2 macrophages are not a homogeneous population but are further subdivided into M2a, M2b, M2c, and M2d subtypes based on their inducing signals and functional characteristics ( Macrophages can polarize into either pro-inflammatory M1 or anti-inflammatory M2 phenotypes in response to distinct environmental cues
