Functional development of mechanosensitive hair cells in stem cell-derived organoids parallels native vestibular hair cells.
Functional development of mechanosensitive hair cells in stem cell-derived organoids parallels native vestibular hair cells.
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DOI：
10.1038/ncomms11508
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发表时间：
2016-05-24
影响因子：
16.6
通讯作者：
Holt JR
中科院分区：
文献类型：
--
作者：
Liu XP;Koehler KR;Mikosz AM;Hashino E;Holt JR
Inner ear sensory epithelia contain mechanosensitive hair cells that transmit information to the brain through innervation with bipolar neurons. Mammalian hair cells do not regenerate and are limited in number. Here we investigate the potential to generate mechanosensitive hair cells from mouse embryonic stem cells in a three-dimensional (3D) culture system. The system faithfully recapitulates mouse inner ear induction followed by self-guided development into organoids that morphologically resemble inner ear vestibular organs. We find that organoid hair cells acquire mechanosensitivity equivalent to functionally mature hair cells in postnatal mice. The organoid hair cells also progress through a similar dynamic developmental pattern of ion channel expression, reminiscent of two subtypes of native vestibular hair cells. We conclude that our 3D culture system can generate large numbers of fully functional sensory cells which could be used to investigate mechanisms of inner ear development and disease as well as regenerative mechanisms for inner ear repair. Sensory hair cells from the mammalian inner ear do not regenerate. Here, the authors induce direct hair cell formation from mouse embryonic stem cells using a three-dimensional culture system and observe differentiation of Type I and Type II vestibular hair cells and establishment of synapses with neurons.
