DAPT mediates atoh1 expression to induce hair cell-like cells

Area of Science:

• Regenerative Medicine
• Otolaryngology
• Gene Therapy

Background:

• Hearing loss is a degenerative condition caused by a lack of hair cells (HCs), which do not regenerate in mammals.
• Gene therapy and drug delivery offer potential treatments for hearing loss.
• Atoh1 is a key transcription factor for HC differentiation.

Purpose of the Study:

• To investigate the synergistic effect of DAPT and Atoh1 in promoting HC fate and regeneration.
• To evaluate DAPT's role in inhibiting HC apoptosis and inducing new HC formation.

Main Methods:

• Utilized DAPT, a Notch signaling inhibitor, to enhance Atoh1 expression.
• Tested the combined therapy in ependymal cells in vitro.
• Assessed hair cell regeneration in cultured basilar membrane (BM) ex vivo.

Main Results:

• DAPT and Atoh1 synergistically promoted HC fate in ependymal cells.
• The combination therapy induced hair cell regeneration in the cultured basilar membrane.
• DAPT enhanced Atoh1 expression, inhibited HC apoptosis, and promoted new HC formation.

Conclusions:

• DAPT combined with Atoh1 gene therapy shows significant potential for hair cell regeneration.
• This approach offers a promising strategy for treating hearing loss by inducing HC-like cells and preventing apoptosis.