“When hair cells are lost in mature animals, the cells can not be naturally restored, which can lead to permanent hearing loss,” Iyer explained. “In the present study, we looked closer into the possibility of promoting hair cell regeneration in mature animals using cell reprogramming. To study the structure of the hair cell packages generated by reprogramming, Iyer teamed up with Dr. Yeohash Raphaels lab at the University of Michigan to perform scanning electron microscopy imaging on the cochleae of mice conditionally overexpressing these transcription factors. The images clearly showed that the hair cell packages were in accordance with what is observed on inner hair cells during advancement.
Hearing loss describes a decrease in the capability to hear sounds, either partly or entirely. It can be triggered by a range of elements such as direct exposure to loud noise, aging, infection, and certain medical conditions.
Approximately 430 million people globally struggle with disabling hearing loss, and in the United States alone, around 37.5 million grownups report problem hearing. When any part of the ear or the nerves that transfer noise to the brain do not function effectively, hearing loss can take place.
For example, damage to the hair cells in the inner ear can result in hearing loss. According to Dr. Amrita Iyer, a scientist at Baylor College of Medicine and lead author of a brand-new study published in eLife, “these cells enable the brain to identify noises.”
“When hair cells are lost in mature animals, the cells can not be naturally regenerated, which can lead to permanent hearing loss,” Iyer discussed. “In the present study, we looked closer into the possibility of promoting hair cell regrowth in mature animals using cell reprogramming.
Transcription factors promote the expression of certain genes and prevent the expression of others. By changing the pattern of gene expression, the researchers intended to lead cells to a state in which they would regrow hair cells in mature animals comparable to what occurs throughout development.
” We compared the reprogramming performance of the hair cell transcription aspect ATOH1 alone or in combination with 2 other hair cell transcription elements, GFI1 and POU4F3, in mouse non-sensory cells in the cochlea, the part of the inner ear that supports hearing,” Iyer stated. “We did this at two timepoints– eight days after birth and 15 days after birth, examining the extent of hair cell regrowth in mice.”
To study the structure of the hair cell bundles created by reprogramming, Iyer teamed up with Dr. Yeohash Raphaels laboratory at the University of Michigan to carry out scanning electron microscopy imaging on the cochleae of mice conditionally overexpressing these transcription aspects. The images clearly revealed that the hair cell packages remained in accordance with what is observed on inner hair cells during advancement. Additional studies showed that these cells also had some attributes that recommended that they were capable of sensing sound.
” We found that although expressing ATOH1 with hair cell transcription aspects GFI1 and POU4F3 can increase the performance of hair cell reprogramming in older animals compared to ATOH1 alone or GFI1 plus ATOH1, the hair cells produced by reprogramming at 8 days of age– even with three hair cell transcription elements– are considerably less mature than those generated by reprogramming at postnatal the first day,” Iyer stated. “We suggest that reprogramming with several transcription factors is much better able to access the hair cell distinction gene regulative network, but that additional interventions may be required to produce fully grown and totally functional hair cells.”
These findings are essential to advancing the existing understanding of the mammalian inner ear hair cell regeneration process. From a therapeutic viewpoint, transcription factor-mediated reprogramming and the underlying biology related to its function may allow fine-tuning of current gene treatment techniques for long-lasting hearing loss treatment.
Reference: “Cellular reprogramming with GFI1, pou4f3, and atoh1 link epigenetic changes and cell-cell signaling as challenges to hair cell regrowth in fully grown mammals” by Amrita A Iyer, Ishwar Hosamani, John D Nguyen, Tiantian Cai, Sunita Singh, Melissa M McGovern, Lisa Beyer, Hongyuan Zhang, Hsin-I Jen, Rizwan Yousaf, Onur Birol, Jenny J Sun, Russell S Ray, Yehoash Raphael, Neil Segil and Andrew K Groves, 29 November 2022, eLife.DOI: 10.7554/ eLife.79712.
The job was supported by the following grants: RO1 DC014832, R21 OD025327, DC015829 and a Hearing Restoration Project Consortium award from the Hearing Health Foundation. The task was also supported by moneying from a CPRIT Core Facility Support Award (CPRIT-RP180672), NIH grants (P30 CA125123, S10 RR024574, S10OD018033, S10OD025240, s10od023469 and p30ey002520), the R. Jamison and Betty Williams Professorship, the University of Michigan College of Engineering and NSF grant #DMR -1625671.