Fig. 4: PMN-MDSCs from bone marrow share the similar developmental trajectory with neutrophilic lineage during aging, and may partially develop from mature neutrophils.

A, B Velocities derived from the dynamical model for PMN-MDSC generation are projected into a UMAP based embedding. Three types of cells were identified according to previously reported marker genes. Including neutrophil progenitors (Elane, Mpo, Prtn3), mature neutrophils (Camp, Ltf, and Lcn2), and PMN-MDSCs (Cd300c, Il1b, Wfdc17). The gene-averaged flow of neutrophil lineage visualized by velocity streamlines showed that neutrophil progenitors developed into mature neutrophils and then PMN-MDSCs. C–E Dynamical model was used to identify driver genes in PMN-MDSC generation. F Developmental trajectory of neutrophil subsets by pseudotime value. G Distribution of five neutrophil subsets along the developmental trajectory. PMN-MDSCs had the highest pseudotime value and were located at the ending point, whereas the neutrophil progenitors had the lowest pseudotime value and were located at the starting point. H Clustered heat map revealing top 50 genes with the most significant alterations across pseudotime in neutrophil population. I Pseudotime plot illustrating expression of selected marker genes over pseudotime. The neutrophil progenitor markers (Elane, Mpo, Prtn3) exhibited a declining trend across the pseudotime trajectory, the mature neutrophil markers (Camp, Ltf, and Lcn2) demonstrated a distinctive “rising first and then falling” pattern, while PMN-MDSC marker genes (Cd300c, Il1b, Wfdc17) and driver genes (Dck, Tpm4, and Il13ra1) showed an increased trend.