Progenitor Timing Shapes NG2 ‐Glia Fate and Oligodendrocyte Differentiation

ABSTRACT

The developmental identity and fate of NG2‐glia remain debated: are they transient oligodendrocyte precursors or a distinct, self‐renewing glial population? Here, we examined how the temporal origin of progenitors influences NG2‐glia and oligodendrocyte lineages in the dorsal cortex. Using in utero and postnatal StarTrack electroporation at E12, E14, E16, and P0, we lineage‐traced their progeny to P30 and P90, performing a clonal analysis in adult mouse brains. Progenitors labeled at E16 generated significantly larger and more widely dispersed NG2‐glia clones, whose contribution increased from P30 to P90, suggesting enhanced proliferative capacity. In contrast, P0‐derived progenitors showed reduced NG2‐glia maintenance and a strong bias toward oligodendrocyte differentiation, forming larger OL clones. Clonal heterogeneity, including mixed NG2‐glia/OL clones, was observed across all stages but peaked at E16. These results identify E16 as a critical window for NG2‐glia expansion and self‐renewal, while P0 marks a transition toward oligodendrocyte lineage restriction, establishing a developmental framework for adult NG2‐glia heterogeneity and maybe a regenerative potential.