Fig. 3

The regulatory mechanism of non-classical TAMCs. (1) Spleen EMH: Splenic CD11b⁺Gr-1^intLy6C^hi cells expand in the marginal zone of the spleen. Spleen recruits specific HSPCs subpopulation from BM via the CCL2/CCR2 axis, and HSPC differentiates into TAMCs driven by endogenous GM-CSF signals and splenic local education. The AngII-AGTR1A signaling pathway increases the retention of HSPCs in the spleen. (2) Tumors block the default red blood cell differentiation pathway of CD45⁺ EPCs in the spleen. Under the effect of GM-CSF, CD45⁺ EPCs trans-differentiate into EDMCs. (3) During embryogenesis, EMPs are formed in the yolk sac. TRMs are derived from both early wave and late wave EMPs. (4) Cancers use thymic stromal lymphopoietin and G-CSF to mobilize BM pre-B accumulation in the spleen. In tumor microenvironment, pre-B responds to cancer-secreted M-CSF and trans-differentiates into B-MF