Multi-omics and live imaging reveal the cells that initiate hearing cell regeneration

The researchers found that inhibition of the Notch signaling pathway selectively activates a rare and previously unrecognized subgroup of supporting cells known as transdifferentiating Deiters' cells (tDCs). These cells are the first to initiate a change in cell identity and begin converting into sensory hair cells, which are essential for hearing.

Although Notch signaling was inhibited broadly, most supporting cells showed little or no response. This finding points to intrinsic differences in regenerative potential and reveals a rare cell population capable of initiating regeneration.

By combining live imaging with single-cell multi-omics approaches, the researchers identified and characterized this subgroup of Deiters' cells and followed the earliest stages of their transition toward a hair cell fate. The study showed that these cells undergo coordinated transcriptional and enhancer remodeling, while neighboring supporting cells remain unresponsive despite Notch pathway inhibition.

The findings provide new insight into the mechanisms that underlie hair cell regeneration and offer a framework for future studies aimed at promoting sensory cell repair in the inner ear.

Authors: Lama Khalaily, Shahar Kasirer, Rotem Domb, Mi Zhou, Buwei Shao, Shahar Taiber, Ran Elkon, Litao Tao, David Sprinzak, and Karen B. Avraham.

Read the full paper:
https://www.science.org/doi/10.1126/sciadv.aed3887