Fig. 5. G-MDSCs emerge through aberrant differentiation trajectory during cancer.
(A) Neutrophil-specific Monocle analysis on subset of Ly6g+ neutrophil clusters resulted in branched trajectory with 5 distinct Monocle states (color code for each state is indicated) which are named based on respective gene expression profile. (B) Pseudotime plot illustrating expression of selected marker genes over pseudotime with the branch ending in State 1 shown with the dotted line, and the branch ending with state 3 highlighted by the solid line. Neutrophil progenitors are characterized by high levels of Elane, Mpo and Prtn3 (state 4), which bifurcate into mature neutrophils (state 3; Camp, Ltf, Lcn2) on the one branch, and MDSCs (state 1; e.g. CD84) on the other branch. (C) Early G-MDSC transition was marked by high expression of Asprv1, Plscr1 and Pirb. (D) Summary schematic indicates that G-MDSCs emerge from neutrophil progenitor cells via an aberrant form of neutrophil differentiation rather than from mature neutrophils that are reprogrammed into immunosuppressive cells.