Engineering High-Fidelity Human Cochlear Organoids

工程高保真人类耳蜗类器官

基本信息

  • 批准号:
    10641936
  • 负责人:
  • 金额:
    $ 65.68万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2022
  • 资助国家:
    美国
  • 起止时间:
    2022-07-01 至 2027-06-30
  • 项目状态:
    未结题

项目摘要

PROJECT SUMMARY Loss of sensory hair cells and/or innervating neurons in the cochlea causes irreversible hearing loss in humans. However, progress on research for realizing biological restoration of hearing has been hampered due to the paucity of human cochlear tissues. My laboratory recently developed a novel organoid system to generate inner ear sensory epithelia containing functional sensory hair cells from aggregates of human pluripotent stem cells in 3D culture. While these first-generation organoids are a valuable tool for studying human inner ear development, they only generate hair cells with structural and functional properties of native vestibular hair cells and fail to produce any cochlear cell types. Another limitation with our original system is the lack of central nervous system components. To overcome these limitations, we aim at developing a next- generation human microphysiological system that more faithfully recapitulates development of the auditory periphery and brainstem. In Aim 1, we will carry out genetic programming and a small-scale CRISPR screen to increase the number of outer hair cells arising in cochlear organoids. The identity of derived hair cells will be validated by single-cell electrophysiology, electron microscopy and single-cell RNA-sequencing. Additionally, maturation of derived hair cells will be promoted by thyroid hormone treatments. In Aim 2, we will establish novel human cochlear-hindbrain assembloids and assess afferent neural circuit development in these assembloids. In Aim 3, we will develop dynamic/tunable hydrogels and test if introducing a spatial gradient of stiffness in the microenvironment during organoid formation can affect tissue patterning or cellular differentiation. Spatial gradients of signaling molecules will be also introduced in hydrogels to test if the dorso- ventral axis formation can be recapitulated during organoid differentiation. The outcome of this study will provide a paradigm-changing approach for studying normal and pathological development of cochlear hair cells and their ascending neural circuits.
项目概要 耳蜗中感觉毛细胞和/或支配神经元的丧失会导致不可逆的听力损失 人类。然而,实现听力生物恢复的研究进展却因以下原因而受到阻碍: 人类耳蜗组织的缺乏。我的实验室最近开发了一种新型类器官系统 从人类聚集体中产生含有功能性感觉毛细胞的内耳感觉上皮 3D 培养中的多能干细胞。虽然这些第一代类器官是研究的宝贵工具 人类内耳发育时,它们只产生具有天然结构和功能特性的毛细胞 前庭毛细胞并且无法产生任何耳蜗细胞类型。我们原始系统的另一个限制是 缺乏中枢神经系统成分。为了克服这些限制,我们的目标是开发下一代 新一代人体微生理系统,更忠实地再现听觉的发展 外周和脑干。在目标 1 中,我们将进行基因编程和小规模 CRISPR 筛选,以 增加耳蜗类器官中产生的外毛细胞的数量。衍生毛细胞的身份将是 通过单细胞电生理学、电子显微镜和单细胞 RNA 测序进行验证。此外, 甲状腺激素治疗将促进衍生毛细胞的成熟。在目标 2 中,我们将建立 新型人类耳蜗后脑组合体并评估这些神经回路的发育 装配体。在目标 3 中,我们将开发动态/可调水凝胶并测试是否引入空间梯度 类器官形成过程中微环境的硬度会影响组织模式或细胞 差异化。信号分子的空间梯度也将被引入水凝胶中,以测试背侧是否 腹轴的形成可以在类器官分化过程中重现。这项研究的结果将 为研究耳蜗毛的正常和病理发育提供一种改变范式的方法 细胞及其上行神经回路。

项目成果

期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ monograph.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ sciAawards.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ conferencePapers.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ patent.updateTime }}

Eri Hashino其他文献

Eri Hashino的其他文献

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

{{ truncateString('Eri Hashino', 18)}}的其他基金

Engineering High-Fidelity Human Cochlear Organoids
工程高保真人类耳蜗类器官
  • 批准号:
    10535013
  • 财政年份:
    2022
  • 资助金额:
    $ 65.68万
  • 项目类别:
Modeling Genetic Inner Ear Disorders with Human Pluripotent Stem Cells
用人类多能干细胞模拟遗传性内耳疾病
  • 批准号:
    9214594
  • 财政年份:
    2016
  • 资助金额:
    $ 65.68万
  • 项目类别:
Modeling Genetic Inner Ear Disorders with Human Pluripotent Stem Cells
用人类多能干细胞模拟遗传性内耳疾病
  • 批准号:
    10062940
  • 财政年份:
    2016
  • 资助金额:
    $ 65.68万
  • 项目类别:
Modeling Inner Ear Differentiation with Pluripotent Stem cells
用多能干细胞模拟内耳分化
  • 批准号:
    8915311
  • 财政年份:
    2014
  • 资助金额:
    $ 65.68万
  • 项目类别:
Modeling Inner Ear Differentiation with Pluripotent Stem Cells
用多能干细胞模拟内耳分化
  • 批准号:
    10394804
  • 财政年份:
    2014
  • 资助金额:
    $ 65.68万
  • 项目类别:
Modeling Inner Ear Differentiation with Pluripotent Stem cells
用多能干细胞模拟内耳分化
  • 批准号:
    8696409
  • 财政年份:
    2014
  • 资助金额:
    $ 65.68万
  • 项目类别:
Modeling Inner Ear Differentiation with Pluripotent Stem Cells
用多能干细胞模拟内耳分化
  • 批准号:
    9916726
  • 财政年份:
    2014
  • 资助金额:
    $ 65.68万
  • 项目类别:
Modeling Inner Ear Differentiation with Pluripotent Stem Cells
用多能干细胞模拟内耳分化
  • 批准号:
    10615050
  • 财政年份:
    2014
  • 资助金额:
    $ 65.68万
  • 项目类别:
Induced Pluripotent Stem Cells for Modeling Congenital Deafness
用于模拟先天性耳聋的诱导多能干细胞
  • 批准号:
    8663875
  • 财政年份:
    2013
  • 资助金额:
    $ 65.68万
  • 项目类别:
Induced Pluripotent Stem Cells for Modeling Congenital Deafness
用于模拟先天性耳聋的诱导多能干细胞
  • 批准号:
    8510855
  • 财政年份:
    2013
  • 资助金额:
    $ 65.68万
  • 项目类别:

相似海外基金

Hormone therapy, age of menopause, previous parity, and APOE genotype affect cognition in aging humans.
激素治疗、绝经年龄、既往产次和 APOE 基因型会影响老年人的认知。
  • 批准号:
    495182
  • 财政年份:
    2023
  • 资助金额:
    $ 65.68万
  • 项目类别:
Investigating how alternative splicing processes affect cartilage biology from development to old age
研究选择性剪接过程如何影响从发育到老年的软骨生物学
  • 批准号:
    2601817
  • 财政年份:
    2021
  • 资助金额:
    $ 65.68万
  • 项目类别:
    Studentship
RAPID: Coronavirus Risk Communication: How Age and Communication Format Affect Risk Perception and Behaviors
RAPID:冠状病毒风险沟通:年龄和沟通方式如何影响风险认知和行为
  • 批准号:
    2029039
  • 财政年份:
    2020
  • 资助金额:
    $ 65.68万
  • 项目类别:
    Standard Grant
Neighborhood and Parent Variables Affect Low-Income Preschool Age Child Physical Activity
社区和家长变量影响低收入学龄前儿童的身体活动
  • 批准号:
    9888417
  • 财政年份:
    2019
  • 资助金额:
    $ 65.68万
  • 项目类别:
The affect of Age related hearing loss for cognitive function
年龄相关性听力损失对认知功能的影响
  • 批准号:
    17K11318
  • 财政年份:
    2017
  • 资助金额:
    $ 65.68万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Affect regulation and Beta Amyloid: Maturational Factors in Aging and Age-Related Pathology
影响调节和 β 淀粉样蛋白:衰老和年龄相关病理学中的成熟因素
  • 批准号:
    9320090
  • 财政年份:
    2017
  • 资助金额:
    $ 65.68万
  • 项目类别:
Affect regulation and Beta Amyloid: Maturational Factors in Aging and Age-Related Pathology
影响调节和 β 淀粉样蛋白:衰老和年龄相关病理学中的成熟因素
  • 批准号:
    10166936
  • 财政年份:
    2017
  • 资助金额:
    $ 65.68万
  • 项目类别:
Affect regulation and Beta Amyloid: Maturational Factors in Aging and Age-Related Pathology
影响调节和 β 淀粉样蛋白:衰老和年龄相关病理学中的成熟因素
  • 批准号:
    9761593
  • 财政年份:
    2017
  • 资助金额:
    $ 65.68万
  • 项目类别:
How age dependent molecular changes in T follicular helper cells affect their function
滤泡辅助 T 细胞的年龄依赖性分子变化如何影响其功能
  • 批准号:
    BB/M50306X/1
  • 财政年份:
    2014
  • 资助金额:
    $ 65.68万
  • 项目类别:
    Training Grant
Inflamm-aging: What do we know about the effect of inflammation on HIV treatment and disease as we age, and how does this affect our search for a Cure?
炎症衰老:随着年龄的增长,我们对炎症对艾滋病毒治疗和疾病的影响了解多少?这对我们寻找治愈方法有何影响?
  • 批准号:
    288272
  • 财政年份:
    2013
  • 资助金额:
    $ 65.68万
  • 项目类别:
    Miscellaneous Programs
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了