Department of Stem Cell and Regenerative Medicine, University of Southern California, Los Angeles, United States; Eli and Edythe Broad Center, University of Southern California, Los Angeles, United States; Zilkha Neurogenetic Institute, University of Southern California, Los Angeles, United States
Talon Trecek
Department of Stem Cell and Regenerative Medicine, University of Southern California, Los Angeles, United States; Eli and Edythe Broad Center, University of Southern California, Los Angeles, United States
Suhasni Gopalakrishnan
Department of Stem Cell and Regenerative Medicine, University of Southern California, Los Angeles, United States; Eli and Edythe Broad Center, University of Southern California, Los Angeles, United States; Zilkha Neurogenetic Institute, University of Southern California, Los Angeles, United States
Litao Tao
Department of Stem Cell and Regenerative Medicine, University of Southern California, Los Angeles, United States; Eli and Edythe Broad Center, University of Southern California, Los Angeles, United States
Alexander L Markowitz
Zilkha Neurogenetic Institute, University of Southern California, Los Angeles, United States; USC Caruso Department of Otolaryngology – Head and Neck Surgery, University of Southern California, Los Angeles, United States
Haoze V Yu
Department of Stem Cell and Regenerative Medicine, University of Southern California, Los Angeles, United States; Eli and Edythe Broad Center, University of Southern California, Los Angeles, United States
Xizi Wang
Department of Stem Cell and Regenerative Medicine, University of Southern California, Los Angeles, United States; Eli and Edythe Broad Center, University of Southern California, Los Angeles, United States
Juan Llamas
Department of Stem Cell and Regenerative Medicine, University of Southern California, Los Angeles, United States; Eli and Edythe Broad Center, University of Southern California, Los Angeles, United States
Zilkha Neurogenetic Institute, University of Southern California, Los Angeles, United States; USC Caruso Department of Otolaryngology – Head and Neck Surgery, University of Southern California, Los Angeles, United States
Justin Ichida
Department of Stem Cell and Regenerative Medicine, University of Southern California, Los Angeles, United States; Eli and Edythe Broad Center, University of Southern California, Los Angeles, United States; Zilkha Neurogenetic Institute, University of Southern California, Los Angeles, United States
Department of Stem Cell and Regenerative Medicine, University of Southern California, Los Angeles, United States; Eli and Edythe Broad Center, University of Southern California, Los Angeles, United States; USC Caruso Department of Otolaryngology – Head and Neck Surgery, University of Southern California, Los Angeles, United States
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 factors (Six1, Atoh1, Pou4f3, and Gfi1) that can convert mouse embryonic fibroblasts, adult tail-tip fibroblasts and postnatal supporting cells into induced hair cell-like 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.
