Genetic blueprint of inner ear cell development created

Scientists have used a sensitive new technology to create the first high-resolution gene expression map of the newborn mouse inner ear.
The findings provide new insight into how epithelial cells in the inner ear develop and differentiate into specialised cells that serve critical functions for hearing and maintaining balance.
Understanding how these important cells form may provide a foundation for the potential development of cell-based therapies for treating hearing loss and balance disorders.
The research was conducted by scientists at the National Institute on Deafness and Other Communication Disorders (NIDCD), part of the US National Institutes of Health.
In a companion study led by NIDCD-supported scientists at the University of Maryland School of Medicine and scientists at the Sackler School of Medicine at Tel Aviv University, researchers used a similar technique to identify a family of proteins critical for the development of inner ear cells.

To gain a better understanding of inner ear cell development, Matthew Kelley, chief of the Section on Developmental Neuroscience at the NIDCD, and his research team used single-cell RNA-seq, a new technology that can extract comprehensive gene activity data from just one cell.

Kelley's team analysed 301 cells - some hair cells and some supporting cells - taken from the cochlea and utricle of newborn mice.
By comparing the cells' gene activity profiles, the researchers found unique patterns in hair cells and supporting cells. They also uncovered evidence for subgroups of cells within each of these classes.
The data also allowed the scientists to identify distinct developmental patterns of gene activity. Cells in the vestibular part of the inner ear develop at somewhat different rates, so each cell was at a slightly different point in its maturity when the researchers examined it.

By analysing the cells' gene activity profiles, the scientists were able to identify genes that are active at each stage of development, bringing to light important clues about how the specialised hair cells are formed.
In the second study, researchers again took advantage of RNA-seq technology. They used a computational-experimental approach to search for common regulatory regions in the genes expressed in the hair cells.
The scientists found that a group of gene regulators called Regulatory Factor Xs (RFX) helps to drive genes that are preferentially active in hair cells.
The researchers found that RFX genes have an essential role in hearing. Mice lacking two RFX proteins began to lose their hair cells and their hearing about two weeks after birth. After three months, these mice were completely deaf.

The researchers concluded that the RFX gene regulators, while not crucial early in the development of hair cells, are necessary for the cells' maturation and long-term survival.
The studies were published in the journal Nature Communications.