Figure 4. Lineage tracing of Sox2⁺ cells at a single cell level.

Sox2-GFP/Cre retrovirus was injected into the dentate gyrus of ROSA26R mice to activate a reporter (β-gal or GFP reporter), which was used to trace the fate of progeny of Sox2⁺ cells. The majority of clones were single-cell clusters showing that targeted Sox2⁺ cells (GFP⁺ or β-gal⁺ cells) became a neuron (A, NeuN⁺), an astrocyte (B, GFAP⁺) or a NSC. Sox2⁺ cells were able to give rise to multiple NSCs (C, SOX2⁺, arrow and arrowhead) or neurons (D, NeuN⁺, arrow and arrowhead) in the hippocampus. Multi-cell clusters containing heterogeneous cell populations were also identified. One clone showed Sox2⁺ NSC could give rise to one neuron (NeuN⁺, arrow) and one astrocyte (GFAP⁺, arrowhead) (E). Some clones contained a Sox2⁺ NSC (SOX2⁺, arrowhead) and a neuron (NeuN⁺, arrow) that were physically associated each other (F). Sox2⁺ NSC was able to give rise to a neuron (NeuN⁺, right arrow) and a Sox2⁺ NSC (SOX2⁺, left arrow) that has GFAP expression (two arrowheads) in the radial process (G). Abbreviations: s, subgranular zone; g, granular layer; m, molecular layer. Scale bar: 10 μm.