Recent studies from our laboratory have highlighted the heterogeneity of tissue macrophages, including significant differences in the gene expression patterns and enhancer landscapes of ileal and colonic macrophages. This might result from their differential exposure to microbiota or factors released by neighboring cells, such as epithelium. To define key factors that establish the distinct macrophage identities, we engraft mice, whose intestinal macrophages have been depleted, with monocytes that express a GFP reporter. This enables us to detect and isolate grafted cells by flow cytometry and ensures that the cells we retrieve from the intestine are synchronized with respect to their development. We have isolated and collected cells from the lamina propria of the colon and the ileum of mice at different days post-transfer and subjected them to RNAseq. We will report the comparison of their expression profiles, as well as the dynamics of transcription factors and their respective targets during monocyte differentiation.