Effects of genetic correction on the differentiation of hair cell-like cells from iPSCs with MYO15A mutation

JR Chen, ZH Tang, J Zheng, HS Shi, J Ding… - Cell Death & …, 2016 - nature.com
JR Chen, ZH Tang, J Zheng, HS Shi, J Ding, XD Qian, C Zhang, JL Chen, CC Wang, L Li…
Cell Death & Differentiation, 2016nature.com
Deafness or hearing loss is a major issue in human health. Inner ear hair cells are the main
sensory receptors responsible for hearing. Defects in hair cells are one of the major causes
of deafness. A combination of induced pluripotent stem cell (iPSC) technology with genome-
editing technology may provide an attractive cell-based strategy to regenerate hair cells and
treat hereditary deafness in humans. Here, we report the generation of iPSCs from members
of a Chinese family carrying MYO15A c. 4642G> A and c. 8374G> A mutations and the …
Abstract
Deafness or hearing loss is a major issue in human health. Inner ear hair cells are the main sensory receptors responsible for hearing. Defects in hair cells are one of the major causes of deafness. A combination of induced pluripotent stem cell (iPSC) technology with genome-editing technology may provide an attractive cell-based strategy to regenerate hair cells and treat hereditary deafness in humans. Here, we report the generation of iPSCs from members of a Chinese family carrying MYO15A c. 4642G> A and c. 8374G> A mutations and the induction of hair cell-like cells from those iPSCs. The compound heterozygous MYO15A mutations resulted in abnormal morphology and dysfunction of the derived hair cell-like cells. We used a CRISPR/Cas9 approach to genetically correct the MYO15A mutation in the iPSCs and rescued the morphology and function of the derived hair cell-like cells. Our data demonstrate the feasibility of generating inner ear hair cells from human iPSCs and the functional rescue of gene mutation-based deafness by using genetic correction.
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