Author response: Generation of inner ear hair cells by direct lineage conversion of primary somatic cells [peer_review]

Louise Menendez, Talon Trecek, Suhasni Gopalakrishnan, Litao Tao, Alexander L Markowitz, Haoze V Yu, Xizi Wang, Juan Llamas, Chichou Huang, James Lee, Radha Kalluri, Justin Ichida (+1 others)
2020 unpublished
The mechanoreceptive sensory hair cells in the inner ear are selectively vulnerable to numerous genetic and environmental insults. In mammals, hair cells lack regenerative capacity, and their death leads to permanent hearing loss and vestibular dysfunction. Their paucity and inaccessibility has limited the search for otoprotective and regenerative strategies. Growing hair cells in vitro would provide a route to overcome this experimental bottleneck. We report a combination of four transcription
more » ... four transcription factors (Six1, Atoh1, Pou4f3, and Gfi1) that can convert mouse embryonic fibroblasts, adult tail-tip fibroblasts and postnatal supporting cells into induced hair celllike cells (iHCs). iHCs exhibit hair cell-like morphology, transcriptomic and epigenetic profiles, electrophysiological properties, mechanosensory channel expression, and vulnerability to ototoxin in a high-content phenotypic screening system. Thus, direct reprogramming provides a platform to identify causes and treatments for hair cell loss, and may help identify future gene therapy approaches for restoring hearing.
doi:10.7554/elife.55249.sa2 fatcat:qdsfjay5kvb7vn3ulnsx635wla