Eri Hashino 及其同事建立了在三維培養(yǎng)中實現內耳感覺上皮細胞從小鼠胚胎干細胞逐步分化的一個新方法,。該過程模仿正常發(fā)育：來自干細胞的毛細胞具有機械感應毛細胞的功能特點，它們與也是從培養(yǎng)中的胚胎干細胞得到的感覺神經元形成突觸,。這一新方法可被用來研究內耳發(fā)育,，同時也許還能為疾病模擬,、藥物發(fā)現和細胞療法實驗提供生成毛細胞的一個手段。（生物谷Bioon.com）
生物谷推薦英文摘要：
Nature doi:10.1038/nature12298
Generation of inner ear sensory epithelia from pluripotent stem cells in 3D culture
Karl R. Koehler, Andrew M. Mikosz, Andrei I. Molosh, Dharmeshkumar Patel & Eri Hashino
The inner ear contains sensory epithelia that detect head movements, gravity and sound. It is unclear how to develop these sensory epithelia from pluripotent stem cells, a process that will be critical for modelling inner ear disorders or developing cell-based therapies for profound hearing loss and balance disorders. So far, attempts to derive inner ear mechanosensitive hair cells and sensory neurons have resulted in inefficient or incomplete phenotypic conversion of stem cells into inner-ear-like cells. A key insight lacking from these previous studies is the importance of the non-neural and preplacodal ectoderm, two critical precursors during inner ear development. Here we report the stepwise differentiation of inner ear sensory epithelia from mouse embryonic stem cells (ESCs) in three-dimensional culture. We show that by recapitulating in vivo development with precise temporal control of signalling pathways, ESC aggregates transform sequentially into non-neural, preplacodal and otic-placode-like epithelia. Notably, in a self-organized process that mimics normal development, vesicles containing prosensory cells emerge from the presumptive otic placodes and give rise to hair cells bearing stereocilia bundles and a kinocilium. Moreover, these stem-cell-derived hair cells exhibit functional properties of native mechanosensitive hair cells and form specialized synapses with sensory neurons that have also arisen from ESCs in the culture. Finally, we demonstrate how these vesicles are structurally and biochemically comparable to developing vestibular end organs. Our data thus establish a new in vitro model of inner ear differentiation that can be used to gain deeper insight into inner ear development and disorder.
