A Developmental Atlas of Mouse Vestibular-Like Inner Ear Organoids

Inner ear sensory epithelia can be generated in vitro from embryonic stem cells. The resulting inner ear organoids represent a potentially inexhaustible source of otic tissues, including sensory hair cells and supporting cells, for in vitro manipulation. Here, we present a single-cell atlas of whole mouse embryonic stem cell-derived vestibular-like inner ear organoids at six developmental stages. Our analyses trace the genesis and developmental progression of otic progenitor cells to supporting cells and hair cells. By profiling all organoid cells, we also characterize the development of additional cell groups, such as otic mesenchyme. We further utilize our atlas to describe a proliferative phase where otic progenitors produce hair cells and otic neuroblasts, followed by a transition to a non-proliferative state. The resulting map of otic progression reveals specific time windows that can inform future research on cell cycle regulation and cell lineage specification in inner ear organoids.可通过体外诱导胚胎干细胞（embryonic stem cells）生成内耳感觉上皮。由此获得的内耳类器官可作为可用于体外操作的近乎无限的耳组织来源，涵盖感觉毛细胞与支持细胞等多种耳源性细胞。本研究构建了小鼠胚胎干细胞来源的前庭样内耳类器官六个发育阶段的全细胞单细胞转录组图谱。通过分析该图谱，我们追踪了耳祖细胞（otic progenitor cells）向支持细胞与毛细胞的发生及发育进程。此外，通过对所有类器官细胞进行全景式转录组分析，本研究还解析了耳间充质等其他细胞类群的发育特征。本研究进一步利用该单细胞转录组图谱，描述了耳祖细胞增殖产生毛细胞与耳成神经细胞（otic neuroblasts）的增殖阶段，以及随后向非增殖状态的转变过程。本研究所构建的耳发育进程图谱揭示了特定的关键时间窗口，可为未来内耳类器官的细胞周期调控与细胞谱系特化研究提供重要参考依据。