Generation of inner ear organoids containing functional hair cells from human pluripotent stem cells
Karl R. Koehler,Jing Nie,Emma Longworth-Mills,Xiao Ping Liu,Jiyoon Lee,Jeffrey R. Holt,Eri Hashino +6 more
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A method for differentiating human pluripotent stem cells to inner ear organoids that harbor functional hair cells and it is demonstrated that derived hair cells exhibit electrophysiological properties similar to those of native sensory hair cells.Abstract:
The derivation of human inner ear tissue from pluripotent stem cells would enable in vitro screening of drug candidates for the treatment of hearing and balance dysfunction and may provide a source of cells for cell-based therapies of the inner ear. Here we report a method for differentiating human pluripotent stem cells to inner ear organoids that harbor functional hair cells. Using a three-dimensional culture system, we modulate TGF, BMP, FGF, and WNT signaling to generate multiple otic-vesicle-like structures from a single stem-cell aggregate. Over 2 months, the vesicles develop into inner ear organoids with sensory epithelia that are innervated by sensory neurons. Additionally, using CRISPR-Cas9, we generate an ATOH1-2A-eGFP cell line to detect hair cell induction and demonstrate that derived hair cells exhibit electrophysiological properties similar to those of native sensory hair cells. Our culture system should facilitate the study of human inner ear development and research on therapies for diseases of the inner ear.read more
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Retrograde ERK activation waves drive base-to-apex multicellular flow in murine cochlear duct morphogenesis.
TL;DR: In this paper, the authors show that extracellular signal-regulated kinase (ERK) activation waves control collective cell migration during the murine cochlear duct development using deep tissue live-cell imaging, Forster resonance energy transfer (FRET)-based quantitation, and mathematical modeling.
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One-dimensional screw-like MoS2 with oxygen partially replacing sulfur as an electrocatalyst for the N2 reduction reaction
TL;DR: In this paper , a screw-like MoS2 with oxygen partially replacing sulfur (1D-MoS2-xOy) nanosheets was synthesized by a one-step solvothermal method as an efficient nonnoble metal electrocatalyst for NRR.
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Modeling human early otic sensory cell development with induced pluripotent stem cells
TL;DR: Modulating Notch pathway during in vitro differentiation of hiPSC-derived otic/placodal progenitors is a valuable strategy to promote the expression of human otic sensory lineage genes.
Book ChapterDOI
Generation of inner ear organoids from human pluripotent stem cells
Jing Nie,Eri Hashino +1 more
TL;DR: An in vitro 3D differentiation method is described, by which the inner ear sensory epithelium harboring hair cells are derived from human pluripotent stem cells (hPSCs), which provide a powerful in vitro platform for studying human inner ear disease and development.
Journal ArticleDOI
Understanding Molecular Evolution and Development of the Organ of Corti Can Provide Clues for Hearing Restoration.
TL;DR: Foxg1 and Lmx1a mutants that radically alter the OC cell assembly and its innervation when mutated and may have driven the evolutionary reorganization of the basilar papilla into an OC in ancestral Therapsids are reported on.
References
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Journal ArticleDOI
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