Phagocytes of mouse, tunicate, and sponge are transcriptionally similar to a unicellular organism. (A) Phylogenetic tree of mouse, tunicate, sponge, choanoflagellate, Capsaspora, Ichthyosporea, and fungi. (B-C) Heat map with Pearson correlation of various mouse cell lineages and Capsaspora. Gene expression profiles were compared among 3 stages of Capsaspora and 30 mouse lineages (B) or 15 lineages (C) based on 3237 conserved homologs. Transcriptome data examined by RNA-seq (B) or CAGE method (C) were analyzed. (D) PC analyses of various lineages or stages of 4 species: Capsaspora, sponge, tunicate, and mouse. Expression levels of 3237 conserved homologs were normalized and compared. (E) Venn diagrams with the number of highly expressed genes in Capsaspora filopodial stage or mouse macrophages compared with mouse ESCs. (F) Frequency of genes shared by various mouse cell lineages among 325 highly expressed genes in Capsaspora filopodial stage. Statistical significance of differences between macrophage and the other lineages are also shown. (G) Frequency of phagocytosis-related genes among 325 genes highly expressed in Capsaspora filopodial stage and 2252 genes low expressed in Capsaspora filopodial stage compared with mouse ESCs. Frequency of phagocytosis- and lysosome-related genes expressed higher in mouse macrophages than mouse ESCs are shown. Frequency of genes highly expressed in macrophages compared to mouse ESCs and nonphagocytic blood cells are shown in red and black, respectively. (H) Cytology of mouse phagocyte (left) and Capsaspora (right) was examined by Wright-Giemsa staining. (I-J) Phagocytic activity of Capsaspora was evaluated by engulfment of pHrodo-green beads (I), and frequency of phagocytic cells was evaluated by flow cytometry (J). Data are representative of 2 independent experiments. ∗P < .05, ∗∗P < .01, ∗∗∗∗P < .0001. ESCs, embryonic stem cells; PtC, peritoneal cavity.