A Blueprint of Cell Development in the Inner Ear

Hair cells (red) and associated supporting cells (green) in the sensory patch of a mouse utricle, part of the balancing apparatus of the inner ear.Dr. Joseph Burns, NIDCD.

The inner ear detects head movements, gravity, and sound using specialized epithelial cells, including hair cells and supporting cells. These cells work together in the inner ear’s snail-shaped cochlea to detect sound. In the fluid-filled utricle—part of the body’s vestibular system, which provides our sense of balance—the cells help detect the head’s movement and position.

In humans, hair cells and supporting cells can’t naturally repair themselves. Damage to the cells can be caused by medications, disease, injury, or aging. The resulting hearing loss and balance problems often can’t be effectively treated. Studying these sensory cells has been difficult, as there are only a few thousand of them and they are tucked deep in a bony channel.

To gain a better understanding of cell development in the inner ear, a research team led by Dr. Matthew Kelley at NIH’s National Institute on Deafness and Other Communication Disorders (NIDCD) studied the inner ear of newborn mice. The scientists used microfluidic technology to capture 301 cells—some hair cells and some supporting cells—taken from the cochlea and utricle of the mice. They analyzed the gene activity of each individual cell using single-cell RNA sequencing (RNA-seq) technology. The study was published on October 15, 2015, in Nature Communications.

The researchers found unique gene activity profiles in hair cells and supporting cells. They also uncovered evidence for subgroups within these broad cell classes. The team speculates that the distinct gene activity patterns they found may reflect specialized, as yet undefined, cell functions.

The scientists were also able to identify genes that are active at each stage of development, bringing to light important clues about how specialized hair cells are formed. Notably, the researchers didn’t find a strict boundary between the sensory and nonsensory regions of these inner ear structures. The data suggest there may be a transitional zone where cells can readily switch fates. This finding has implications for the potential development of cell-based therapies to treat hearing loss and balance disorders.

In a companion study, an NIH-supported team led by Dr. Ronna Hertzano at the University of Maryland School of Medicine used RNA-seq to identify a family of gene-regulating proteins called regulatory factor Xs (RFX) that are active in hair cells. While not crucial for early hair cell development, these regulators are necessary for the cells’ long-term survival. Mice lacking 2 RFX proteins became deaf within 3 months of birth.

Understanding the networks that control the development of the inner ear could one day lead to therapies for treating hearing loss and balance problems. “Identifying the gene expression maps for the development of inner ear cells is essential to understanding how they form, and may help us create ways to regenerate these cells,” Kelley says.