Fig. 5: M-MDSCs from bone marrow share a similar developmental trajectory with monocytic lineage during aging, and may partially develop from mature monocytes.

A, B Velocities derived from the dynamical model for M-MDSC generation are projected into a UMAP based embedding. Four types of cells were identified according to previously reported marker genes. Including hematopoietic stem/progenitor cells (Cenpf, Mki67, and Top2a), mature monocytes (Ccr2, Csf1r, Cx3cr1), frailty-specific monocytes (Malat1, Neat1) and PMN-MDSCs (Cd300c, Il1b, Retnlg). C–E Dynamical model was used to identify driver genes in M-MDSC generation. F Developmental trajectory of monocyte subsets by pseudotime value. G Distribution of five monocyte subsets along the developmental trajectory. M-MDSCs had the highest pseudotime value and were located at the ending point, whereas the hematopoietic stem/progenitor cells (HSPCs) had the lowest pseudotime value and were located at the starting point. H Clustered heatmap revealing top 50 genes with the most significant alterations across pseudotime in monocyte population. I Pseudotime plot illustrating expression of selected marker genes over pseudotime. The hematopoietic stem/progenitor cell markers (Cenpf, Mki67, Top2a) exhibited a declining trend across the pseudotime trajectory, the mature monocyte markers (Ccr2, Csf1r, Cx3cr1) demonstrated a “rising first and then falling” pattern, while M-MDSC marker genes (Cd300c, Il1b, Retnlg) and driver genes (C5ar1, Dgat1, Retreg1) showed an increased trend.