Waldhaus Joerg, Jiang Linghua, Liu Liqian, Liu Jie, Duncan Robert Keith
Department of Otolaryngology-Head and Neck Surgery, Kresge Hearing Research Institute, University of Michigan, Ann Arbor, MI, USA.
Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI, USA.
iScience. 2024 Feb 1;27(3):109069. doi: 10.1016/j.isci.2024.109069. eCollection 2024 Mar 15.
Inner ear organoids recapitulate development and are intended to generate cell types of the otic lineage for applications such as basic science research and cell replacement strategies. Here, we use single-cell sequencing to study the cellular heterogeneity of late-stage mouse inner ear organoid sensory epithelia, which we validated by comparison with datasets of the mouse cochlea and vestibular epithelia. We resolved supporting cell sub-types, cochlear-like hair cells, and vestibular type I and type II-like hair cells. While cochlear-like hair cells aligned best with an outer hair cell trajectory, vestibular-like hair cells followed developmental trajectories similar to programs branching into type II and then type I extrastriolar hair cells. These results highlight the transcriptional accuracy of the organoid developmental program but will also inform future strategies to improve synaptic connectivity and regional specification.
内耳类器官重现了发育过程,旨在生成耳谱系的细胞类型,用于基础科学研究和细胞替代策略等应用。在这里,我们使用单细胞测序来研究晚期小鼠内耳类器官感觉上皮的细胞异质性,并通过与小鼠耳蜗和前庭上皮的数据集进行比较来验证。我们解析出了支持细胞亚型、耳蜗样毛细胞以及前庭I型和II型样毛细胞。虽然耳蜗样毛细胞与外毛细胞轨迹最匹配,但前庭样毛细胞遵循的发育轨迹类似于分支为II型然后是I型纹外毛细胞的程序。这些结果突出了类器官发育程序的转录准确性,但也将为未来改善突触连接和区域特化的策略提供信息。