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以单细胞分辨率绘制小鼠内耳类器官的发育潜能

Mapping the developmental potential of mouse inner ear organoids at single-cell resolution.

作者信息

Waldhaus Joerg, Jiang Linghua, Liu Liqian, Liu Jie, Duncan Robert Keith

机构信息

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.

出版信息

iScience. 2024 Feb 1;27(3):109069. doi: 10.1016/j.isci.2024.109069. eCollection 2024 Mar 15.

DOI:10.1016/j.isci.2024.109069
PMID:38375227
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10875570/
Abstract

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.

摘要

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。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2ab0/10875570/c4f92026e995/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2ab0/10875570/779e0f6a1020/fx1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2ab0/10875570/80a22d6ab8cc/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2ab0/10875570/e4b97695a233/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2ab0/10875570/4a51756152c4/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2ab0/10875570/46935f0dbb44/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2ab0/10875570/2609ff568324/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2ab0/10875570/c4f92026e995/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2ab0/10875570/779e0f6a1020/fx1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2ab0/10875570/80a22d6ab8cc/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2ab0/10875570/e4b97695a233/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2ab0/10875570/4a51756152c4/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2ab0/10875570/46935f0dbb44/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2ab0/10875570/2609ff568324/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2ab0/10875570/c4f92026e995/gr6.jpg

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本文引用的文献

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A single-cell level comparison of human inner ear organoids with the human cochlea and vestibular organs.人类内耳类器官与人类耳蜗和前庭器官的单细胞水平比较。
Cell Rep. 2023 Dec 26;42(12):113527. doi: 10.1016/j.celrep.2023.113527. Epub 2023 Nov 29.
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Generating high-fidelity cochlear organoids from human pluripotent stem cells.从人类多能干细胞中生成高保真耳蜗类器官。
Cell Stem Cell. 2023 Jul 6;30(7):950-961.e7. doi: 10.1016/j.stem.2023.06.006.
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Defining developmental trajectories of prosensory cells in human inner ear organoids at single-cell resolution.
视黄酸信号传导指导内耳类器官生成的效率,并控制感觉-非感觉命运的特化。
bioRxiv. 2025 Mar 21:2025.03.21.644434. doi: 10.1101/2025.03.21.644434.
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A developmental atlas of mouse vestibular-like inner ear organoids.小鼠前庭样内耳类器官的发育图谱。
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Metabolic Profiling of Cochlear Organoids Identifies α-Ketoglutarate and NAD as Limiting Factors for Hair Cell Reprogramming.耳蜗类器官的代谢组学分析鉴定出α-酮戊二酸和 NAD 为毛细胞重编程的限制因素。
Adv Sci (Weinh). 2024 Sep;11(34):e2308032. doi: 10.1002/advs.202308032. Epub 2024 Jul 11.
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Development. 2023 Jun 15;150(12). doi: 10.1242/dev.201071. Epub 2023 Jun 29.
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Development and transdifferentiation into inner hair cells require Tbx2.发育以及向内毛细胞的转分化需要Tbx2。
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Follistatin regulates the specification of the apical cochlea responsible for low-frequency hearing in mammals.卵泡抑素调节哺乳动物负责低频听力的耳蜗顶端的特化。
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CHD7 regulates otic lineage specification and hair cell differentiation in human inner ear organoids.CHD7 调控人内耳类器官中耳嵴谱系特化和毛细胞分化。
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Cell-type identity of the avian utricle.禽类囊的细胞类型特征。
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Early Wnt Signaling Activation Promotes Inner Ear Differentiation via Cell Caudalization in Mouse Stem Cell-Derived Organoids.早期 Wnt 信号激活通过小鼠干细胞衍生类器官中的细胞尾部化促进内耳分化。
Stem Cells. 2023 Jan 30;41(1):26-38. doi: 10.1093/stmcls/sxac071.
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Tbx2 is a master regulator of inner versus outer hair cell differentiation.Tbx2 是内毛细胞与外毛细胞分化的主调控因子。
Nature. 2022 May;605(7909):298-303. doi: 10.1038/s41586-022-04668-3. Epub 2022 May 4.