Perivascular localized cells commit erythropoiesis in PDGF‐B‐expressing solid tumors

Using mouse-derived pericytes, genetic tracing (NG2-CreERT2:R26R-tdTomato), FACS, single-cell sequencing, and colony formation assays, the authors investigated whether perivascular localized cells in solid tumors can undergo erythropoiesis. Genome-wide expression profiling revealed that PDGF-B stimulation induced NG2+ perivascular cells to exhibit hematopoietic stem and progenitor-like features with differentiation toward the erythroid lineage. Tumor-derived PDGF-B also stimulated cancer-associated fibroblasts (CAFs) to produce EPO locally within the tumor microenvironment. Genetic tracing experiments confirmed that NG2+ cells expressed erythroblast markers in solid tumors and that tumor-isolated NG2+ cells expressed HSC markers and differentiated into erythrocytes in vitro. These tumor-derived hematopoietic cells were noncanonical, lacking CD45 expression and retaining mesenchymal markers such as NG2. The authors emphasize these are preclinical mouse findings that require validation in other models and clinical samples, noting technical limitations such as potential contamination during single-cell isolation.