Scrap the Hearing Aid: Neurogenesis Within the Cochlear Region

A Potential Solution to Hearing Loss

In Dr. Wei-Ming Yu’s research article, he details how Mafb and Gata3 transcription factors play an important role in the exceptional construction of cochlear neurogenesis. Yu describes how the absence of Gata3 factors affects synapse generation in hair cells located within the ear, and thus contribute to abnormal hearing in lab rodents. However, when specific tests were performed and Mafb was projected into the the lab rodent, the structure that typically forms as a result, called, “ribbon synapses” formed regardless of the absence of Gata3. This is revolutionary because the Gata3 protein, although not as thoroughly researched, is known to be crucial to ribbon synapse development, and by obstructing the development of ribbon synapses due to the protein's absence, one would assume that hair cell generation would be mutated or non-existent. This research allows some insight on the even greater importance of the MafB transcription factor. Hypothetically, if hearing loss is observed in a human subject where Gata3 is absent, and Mafb was strategically projected into the cochlear region, there may be neurogenesis and restoration of hearing.

In coordination with restoring hearing in humans, researchers at Massachusetts Institute of Technology (MIT), Harvard Stem Cell Institute, and Brigham&Women’s Hospital, have experimented with a “drug cocktail” that has (relatively) stem cell-like properties. The original study focused on the regeneration of hair-like cells for intestinal lining. By introducing blank canvases into the intestine, and then exposing them to the specific treatment, the researchers were able to differentiate the cells into specific intestinal lining hair-like cells. Lgr5+ cells, specifically, can be divided into many categories found within the mammalian body, ranging from functions in the ear, stomach, kidneys, intestines, and actual hair follicles. The study proved that the drug mixture can produce or trigger the generation of many stem-cell-like cells that can differentiate according to location and characterization. The mixture of medications, when administered into the ear, triggers a mass generation of blank stem-cells that quickly transform into hair cells.

A foreseen dilemma the researchers feared was based on the surface area of the cochlea. Granted a human cochlea is larger than a mouse cochlea, the hair cells required for exceptional hearing are few and do not regenerate. The implementation of stem-cell-like cells into the cochlear region in the drug cocktail study offers a solution where not only do the Lgr5+ cells adapt and function in the cochlear region, but they also multiple and regenerate phenomenally. “...by exposing Lgr5+ cells isolated from the cochlea of mice to the small molecule cocktail, the researchers were able to create a 2,000-fold increase in the number of stem cells” (McLean, et.al, 2017).

The exciting aspect of both Dr. Yu’s research with MafB& Gata3 being published in 2013, and the drug cocktail research being published in 2017 not only lies in the fact that it is so new to the cellular biology field, but that it also poses as a potential medicinal trial and solution for those suffering from hearing loss.

Work Referenced

Yu, Wei-Ming, et al. “A Gata3–Mafb Transcriptional Network Directs Post-Synaptic Differentiation in Synapses Specialized for Hearing.” ELife, ELife Sciences Publications, Ltd, 10 Dec. 2013,

 www.ncbi.nlm.nih.gov/pmc/articles/PMC3851837/.

Image Link: https://elifesciences.org/articles/01341

Will J. McLean, et al., “Clonal Expansion of Lgr5-Positive Cells from Mammalian Cochlea and High-Purity Generation of Sensory Hair Cells, Cell reports, 2017; doi:10.1016/j.celrep.2017.01.066

http://www.cell.com/cell-reports/pdf/S2211-1247(17)30136-5.pdf