中国核心期刊要目总览
中国科技核心期刊
CSCD数据库源刊
中国科技核心期刊
CSCD数据库源刊
兽类学报 ›› 2025, Vol. 45 ›› Issue (6): 771-783.DOI: 10.16829/j.slxb.151059
张梦蝶1(
), 朱弼成2, 何光林3, 张玉忠3, 简锦婵1, 沈安琪1, 刘芸珠1, 何锴1()
收稿日期:2025-01-23
接受日期:2025-04-27
出版日期:2025-11-30
发布日期:2025-12-03
通讯作者:
何锴
作者简介:张梦蝶 (2001- )，女，硕士研究生，主要从事动物适应性进化研究. E-mail: zmd@e.gzhu.edu.cn
基金资助:
Mengdie ZHANG1(), Bicheng ZHU2, Guanglin HE3, Yuzhong ZHANG3, Jinchan JIAN1, Anqi SHEN1, Yunzhu LIU1, Kai HE1()
Received:2025-01-23
Accepted:2025-04-27
Online:2025-11-30
Published:2025-12-03
Contact:
Kai HE
摘要：
内耳作为听觉和平衡的核心器官，其结构精密复杂，细胞类型丰富多样。单细胞转录组测序技术 (scRNA‑Seq) 能够捕获和分析单个细胞的基因表达谱，为深入解析内耳中各种细胞类型的功能及其分子机制提供了强大的工具。本文系统回顾了2015—2024年scRNA‑Seq在内耳研究领域的重要应用，重点阐述了该技术在揭示细胞异质性、追踪内耳发育过程、探究听力损伤机制以及促进细胞再生研究等方面的重要进展。我们展望了scRNA‑Seq技术在野生哺乳动物研究中可能解决的关键科学问题，以及单细胞多组学技术在揭示哺乳动物内耳的适应性进化与分子机制方面的潜力。
中图分类号:
张梦蝶, 朱弼成, 何光林, 张玉忠, 简锦婵, 沈安琪, 刘芸珠, 何锴. 单细胞转录组测序在哺乳动物内耳研究中的应用前景[J]. 兽类学报, 2025, 45(6): 771-783.
Mengdie ZHANG, Bicheng ZHU, Guanglin HE, Yuzhong ZHANG, Jinchan JIAN, Anqi SHEN, Yunzhu LIU, Kai HE. The prospective applications of single-cell transcriptome sequencing in mammalian inner ear research[J]. ACTA THERIOLOGICA SINICA, 2025, 45(6): 771-783.
研究目的 Research objective | 相关研究 Related research | 方法 Method | 主要发现 Primary findings |
|---|---|---|---|
揭示不同细胞基因表达谱的异质性，发现新的细胞类型和亚型 Uncover the heterogeneity of gene expression profiles across different cells， identifying novel cell types and subtypes | Jean et al.， 2023 | snRNA-Seq； scRNA-Seq | 发现并命名了周围结构1型细胞、周围结构2型细胞和前庭阶边缘细胞 Discovered and named surrounding structures 1 and 2 （SS1， SS2） cells、scala vestibuli border （SVB） cells |
| Petitpré et al.， 2018 | scRNA-Seq | 将Ⅰ型SGN进一步分为SGN Ⅰa、SGN Ⅰb和SGN Ⅰc三个亚型 Further classified typeⅠspiral ganglion neurons （SGN） into three subtypes： SGN Ⅰa， SGN Ⅰb， and SGN Ⅰc | |
| Shrestha et al.， 2018 | scRNA-Seq | ||
| Sun et al.， 2018 | scRNA-Seq | ||
| Wang et al.， 2024 | scRNA-Seq | 发现了一种保守的SGN亚型： Ⅲ型SGN Discovered a conserved SGN subtype： type Ⅲ SGN | |
获得稀有细胞类型表达谱 Obtain expression profiles of rare cell types | Ranum et al.， 2019 | scRNA-Seq | 获取成年小鼠外毛细胞的表达图谱，并发现新的标记基因Ocm和Sri等 Obtained the expression profile of outer hair cells in adult mice and identified new marker genes such as Ocm and Sri |
| Gu et al.， 2020 | snRNA-Seq | 获得根细胞和纺锤体细胞的表达图谱，纺锤体细胞的标记基因 （Anxa1和Dpp10） Obtained expression profiles of root cells and spindle cells， and identified marker genes for spindle cells （Anxa1 and Dpp10） | |
| Taukulis et al.， 2021 | scRNA-Seq | 获取血管纹细胞类型的表达图谱 Obtained expression profiles of cell types in the stria vascularis | |
追踪内耳单细胞发育谱系 Trace the single-cell developmental lineage of the inner ear | Yu et al.， 2019 | scRNA-Seq | 耳蜗发育分为3个阶段：增殖期 （E14.5前）、快速分化期 （E14.5 ~ E18.5） 和成熟期 （E18.5后） Cochlear development is divided into three stages： proliferation stage （before E14.5）， rapid differentiation stage （E14.5 - E18.5）， and maturation stage （after E18.5） |
| Sun et al.， 2022b | scRNA-Seq | 神经母细胞在E11.5时开始分化为SGN和VGN，VGN在E13.5时进一步分化为两种亚型，SGN在E13.5时未开始分化 Neuroblasts begin to differentiate into spiral ganglion neurons （SGN） and vestibular ganglion neurons （VGN） at E11.5； VGN further differentiate into two subtypes at E13.5， while SGN have not begun differentiation at E13.5 | |
| Xu et al.， 2022b | scRNA-Seq | 内毛细胞在P14阶段时发育基本停止，外毛细胞的发育则持续到P28阶段 The development of inner hair cells essentially ceases at P14， the development of outer hair cells continues until P28 | |
| Kolla et al.， 2020 | scRNA-Seq | 揭示从支持细胞到毛细胞的发育轨迹 （E14-P7），抑制Tgfβr1基因导致外毛细胞数量下降 Revealed the developmental trajectory from supporting cells to hair cells （E14-P7）； inhibition of the Tgfβr1 gene led to a decrease in the number of outer hair cells | |
揭示与听力损失相关的细胞类型和基因表达变化 Reveal cell types and gene expression changes associated with hearing loss | Xue et al.， 2021 | GWAS；scRNA-Seq | 82个与年龄相关的听力损失相关SNP在耳蜗的多种细胞类型中均有表达 82 SNPs associated with age-related hearing loss are expressed in multiple cell types of the cochlea |
| Kalra et al.， 2020 | GWAS；scRNA-Seq | 与听力损伤相关的基因如Ankra2、Ccdc68、Synj2和Cdh23等主要在毛细胞中表达 Genes associated with hearing impairment， such as Ankra2， Ccdc68， Synj2， and Cdh23， are primarily expressed in hair cells | |
| Nelson et al.， 2021 | GWAS；scRNA-Seq | SSNHL基因如Sod1等不仅在毛细胞表达，在PC和DC等支持细胞中也表达 Genes associated with sudden sensorineural hearing loss （SSNHL）， such as Sod1， are expressed not only in hair cells but also in supporting cells like pillar cells （PC） and Deiters’ cells （DC） | |
| Tang et al.， 2019 | scRNA-Seq | Tmprss3缺失会破坏细胞内稳态，最终引发毛细胞的变性 Deficiency of Tmprss3 disrupts cellular homeostasis， ultimately leading to degeneration of hair cells | |
| Liu et al.， 2023 | ScISOR-Seq | Otof的转录变体能够翻译功能性蛋白质异构体，最终引发听力损失 Transcript variants of Otof can translate into functional protein isoforms， ultimately causing hearing loss | |
揭示调控毛细胞再生的关键转录因子 Identify key transcription factors regulating hair cell regeneration | Yamashita et al.， 2018 | scRNA-Seq | 发现Pou4f3和Isl1是与毛细胞再生相关的转录因子 Discovered that Pou4f3 and Isl1 are transcription factors associated with hair cell regeneration |
| Iyer et al.， 2022 | scRNA-Seq | 发现Atoh1和Ikzf2是与毛细胞再生相关的转录因子 Discovered that Atoh1 and Ikzf2 are transcription factors associated with hair cell regeneration |
表1 单细胞转录组测序技术在内耳研究领域中的应用
Table 1 Application of single-cell transcriptome sequencing technology in the field of inner ear research
研究目的 Research objective | 相关研究 Related research | 方法 Method | 主要发现 Primary findings |
|---|---|---|---|
揭示不同细胞基因表达谱的异质性，发现新的细胞类型和亚型 Uncover the heterogeneity of gene expression profiles across different cells， identifying novel cell types and subtypes | Jean et al.， 2023 | snRNA-Seq； scRNA-Seq | 发现并命名了周围结构1型细胞、周围结构2型细胞和前庭阶边缘细胞 Discovered and named surrounding structures 1 and 2 （SS1， SS2） cells、scala vestibuli border （SVB） cells |
| Petitpré et al.， 2018 | scRNA-Seq | 将Ⅰ型SGN进一步分为SGN Ⅰa、SGN Ⅰb和SGN Ⅰc三个亚型 Further classified typeⅠspiral ganglion neurons （SGN） into three subtypes： SGN Ⅰa， SGN Ⅰb， and SGN Ⅰc | |
| Shrestha et al.， 2018 | scRNA-Seq | ||
| Sun et al.， 2018 | scRNA-Seq | ||
| Wang et al.， 2024 | scRNA-Seq | 发现了一种保守的SGN亚型： Ⅲ型SGN Discovered a conserved SGN subtype： type Ⅲ SGN | |
获得稀有细胞类型表达谱 Obtain expression profiles of rare cell types | Ranum et al.， 2019 | scRNA-Seq | 获取成年小鼠外毛细胞的表达图谱，并发现新的标记基因Ocm和Sri等 Obtained the expression profile of outer hair cells in adult mice and identified new marker genes such as Ocm and Sri |
| Gu et al.， 2020 | snRNA-Seq | 获得根细胞和纺锤体细胞的表达图谱，纺锤体细胞的标记基因 （Anxa1和Dpp10） Obtained expression profiles of root cells and spindle cells， and identified marker genes for spindle cells （Anxa1 and Dpp10） | |
| Taukulis et al.， 2021 | scRNA-Seq | 获取血管纹细胞类型的表达图谱 Obtained expression profiles of cell types in the stria vascularis | |
追踪内耳单细胞发育谱系 Trace the single-cell developmental lineage of the inner ear | Yu et al.， 2019 | scRNA-Seq | 耳蜗发育分为3个阶段：增殖期 （E14.5前）、快速分化期 （E14.5 ~ E18.5） 和成熟期 （E18.5后） Cochlear development is divided into three stages： proliferation stage （before E14.5）， rapid differentiation stage （E14.5 - E18.5）， and maturation stage （after E18.5） |
| Sun et al.， 2022b | scRNA-Seq | 神经母细胞在E11.5时开始分化为SGN和VGN，VGN在E13.5时进一步分化为两种亚型，SGN在E13.5时未开始分化 Neuroblasts begin to differentiate into spiral ganglion neurons （SGN） and vestibular ganglion neurons （VGN） at E11.5； VGN further differentiate into two subtypes at E13.5， while SGN have not begun differentiation at E13.5 | |
| Xu et al.， 2022b | scRNA-Seq | 内毛细胞在P14阶段时发育基本停止，外毛细胞的发育则持续到P28阶段 The development of inner hair cells essentially ceases at P14， the development of outer hair cells continues until P28 | |
| Kolla et al.， 2020 | scRNA-Seq | 揭示从支持细胞到毛细胞的发育轨迹 （E14-P7），抑制Tgfβr1基因导致外毛细胞数量下降 Revealed the developmental trajectory from supporting cells to hair cells （E14-P7）； inhibition of the Tgfβr1 gene led to a decrease in the number of outer hair cells | |
揭示与听力损失相关的细胞类型和基因表达变化 Reveal cell types and gene expression changes associated with hearing loss | Xue et al.， 2021 | GWAS；scRNA-Seq | 82个与年龄相关的听力损失相关SNP在耳蜗的多种细胞类型中均有表达 82 SNPs associated with age-related hearing loss are expressed in multiple cell types of the cochlea |
| Kalra et al.， 2020 | GWAS；scRNA-Seq | 与听力损伤相关的基因如Ankra2、Ccdc68、Synj2和Cdh23等主要在毛细胞中表达 Genes associated with hearing impairment， such as Ankra2， Ccdc68， Synj2， and Cdh23， are primarily expressed in hair cells | |
| Nelson et al.， 2021 | GWAS；scRNA-Seq | SSNHL基因如Sod1等不仅在毛细胞表达，在PC和DC等支持细胞中也表达 Genes associated with sudden sensorineural hearing loss （SSNHL）， such as Sod1， are expressed not only in hair cells but also in supporting cells like pillar cells （PC） and Deiters’ cells （DC） | |
| Tang et al.， 2019 | scRNA-Seq | Tmprss3缺失会破坏细胞内稳态，最终引发毛细胞的变性 Deficiency of Tmprss3 disrupts cellular homeostasis， ultimately leading to degeneration of hair cells | |
| Liu et al.， 2023 | ScISOR-Seq | Otof的转录变体能够翻译功能性蛋白质异构体，最终引发听力损失 Transcript variants of Otof can translate into functional protein isoforms， ultimately causing hearing loss | |
揭示调控毛细胞再生的关键转录因子 Identify key transcription factors regulating hair cell regeneration | Yamashita et al.， 2018 | scRNA-Seq | 发现Pou4f3和Isl1是与毛细胞再生相关的转录因子 Discovered that Pou4f3 and Isl1 are transcription factors associated with hair cell regeneration |
| Iyer et al.， 2022 | scRNA-Seq | 发现Atoh1和Ikzf2是与毛细胞再生相关的转录因子 Discovered that Atoh1 and Ikzf2 are transcription factors associated with hair cell regeneration |
图1 内耳的结构模式图. A：内耳结构示意图；B、C：耳蜗纵截面示意图；D：柯蒂氏器结构示意图
Fig.1 Structural model of the inner ear. A: Schematic diagram of the inner ear structure; B, C: Schematic diagram of the longitudinal section of the cochlea; D: Schematic diagram of the structure of the organ of Corti
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