Figure 7.

(A) It’s known that sox2+ progenitors that are preserved post neo-induced HC injury divide and differentiate to regenerate HCs. To simulate the situation in mammalian inner ear where the progenitors are absent, we created a severe injury model by exhausting sox2⁺ progenitors with Notch inhibitor and ablating mature HCs with neomycin. We found that the exhausted sox2⁺ progenitors in severe injury have high potential to restore themselves within 48 hr, with HCs being regenerated afterwards. The atoh1a⁺ HC precursors, the main population that survived post severe injury, were converted into proliferative progenitors to initiate regeneration through yap-lin28a pathway. (B) Yap is activated in atoh1a⁺ HC precursors post severe injury and binds directly to lin28a promoter for initiating its transcription. Lin28a activates Wnt pathway through microRNA let7 to promote regenerative proliferation.