Brain-region-specific humanized cortical interneuron mice

脑区域特异性人源化皮质中间神经元小鼠

基本信息

  • 批准号:
    10735991
  • 负责人:
  • 金额:
    $ 66.05万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2023
  • 资助国家:
    美国
  • 起止时间:
    2023-07-01 至 2028-04-30
  • 项目状态:
    未结题

项目摘要

Abstract GABAergic cortical interneurons (cINs) play critical roles in balancing, synchronizing, and gating brain activity by inhibiting other neurons. Their malfunction, especially those of medial ganglionic eminence (MGE)-derived cINs, has been associated with various neurodevelopmental brain disorders, such as schizophrenia (SCZ) and autism spectrum disorders (ASD). Considering the fact that the divergence between human brains and rodent brains has resulted in the failure of many central nervous system (CNS) therapeutics validated in rodent models, it is critical to study human neurons to better understand the mechanisms of these cIN-associated brain disorders. Human fetal brain tissues are not accessible for mechanistic studies, but we have developed a method to efficiently generate homogeneous populations of MGE-type human cINs from pluripotent stem cells (PSCs) of healthy or diseased subjects. We have extensively characterized them and demonstrated their authenticity and functionality, making it possible to study the converging functional consequences of complex genetics in real patient neurons, which cannot be studied in mouse neurons due to a lack of conservation of non-coding regions, where most of risk loci are present. However, in vitro cultured neurons lack other critical components of the brain environment, such as astrocytes, oligodendrocytes, microglia and blood vessels, which can significantly impact their function. There have been efforts to optimize in vitro culture systems to better recapitulate in vivo physiological environments by adding other brain cellular components, but there are still limitations as to how closely they can simulate in vivo situations. To resolve this issue, in our previous study, we pioneered human neuron-mouse brain chimeras to study the function of human SCZ neurons in physiological environments. Although we were able to successfully identify SCZ cIN-intrinsic connectivity deficits in mouse brains, we were not able to analyze the impacts of grafted neurons on brain circuits and behaviors due to the presence of healthy mouse neurons in the grafted mice. Thus, in this proposed study, we will perform brain-region-specific cIN-ablation in NodScid gamma (NSG) mice, followed by the replacement of ablated host cINs with human cINs to generate region-specific humanized cIN chimeras. Based on previous studies, including ours, that show successful restoration of compromised mouse inhibition by grafted human cINs, these mice will allow us to analyze the functional impacts of grafted human cINs on the brain circuits and behaviors in physiological in vivo environments. This novel physiological model system will help us tease apart cell-type- and brain-region-specific disease mechanisms for complex brain disorders, and aid in developing novel therapeutics.
摘要

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 }}

SANGMI CHUNG其他文献

SANGMI CHUNG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('SANGMI CHUNG', 18)}}的其他基金

Common schizophrenia variants functioning in developmental human cortical interneurons
在发育中的人类皮质中间神经元中发挥作用的常见精神分裂症变异
  • 批准号:
    10735990
  • 财政年份:
    2023
  • 资助金额:
    $ 66.05万
  • 项目类别:
Stem Cell-Derived Developmental Human Cortical Interneurons to Treat Intractable Epilepsy
干细胞衍生的发育性人类皮质中间神经元治疗难治性癫痫
  • 批准号:
    10355921
  • 财政年份:
    2021
  • 资助金额:
    $ 66.05万
  • 项目类别:
iPSC derived human cortical interneurons as developmental model of Schizophrenia
iPSC 衍生的人类皮质中间神经元作为精神分裂症的发育模型
  • 批准号:
    8944687
  • 财政年份:
    2015
  • 资助金额:
    $ 66.05万
  • 项目类别:
Isolation and characterization of midbrain dopaminergic neuronal precursors
中脑多巴胺能神经元前体的分离和表征
  • 批准号:
    8494704
  • 财政年份:
    2012
  • 资助金额:
    $ 66.05万
  • 项目类别:
Isolation and characterization of midbrain dopaminergic neuronal precursors
中脑多巴胺能神经元前体的分离和表征
  • 批准号:
    8356550
  • 财政年份:
    2012
  • 资助金额:
    $ 66.05万
  • 项目类别:

相似海外基金

Rational design of rapidly translatable, highly antigenic and novel recombinant immunogens to address deficiencies of current snakebite treatments
合理设计可快速翻译、高抗原性和新型重组免疫原,以解决当前蛇咬伤治疗的缺陷
  • 批准号:
    MR/S03398X/2
  • 财政年份:
    2024
  • 资助金额:
    $ 66.05万
  • 项目类别:
    Fellowship
Re-thinking drug nanocrystals as highly loaded vectors to address key unmet therapeutic challenges
重新思考药物纳米晶体作为高负载载体以解决关键的未满足的治疗挑战
  • 批准号:
    EP/Y001486/1
  • 财政年份:
    2024
  • 资助金额:
    $ 66.05万
  • 项目类别:
    Research Grant
CAREER: FEAST (Food Ecosystems And circularity for Sustainable Transformation) framework to address Hidden Hunger
职业:FEAST(食品生态系统和可持续转型循环)框架解决隐性饥饿
  • 批准号:
    2338423
  • 财政年份:
    2024
  • 资助金额:
    $ 66.05万
  • 项目类别:
    Continuing Grant
Metrology to address ion suppression in multimodal mass spectrometry imaging with application in oncology
计量学解决多模态质谱成像中的离子抑制问题及其在肿瘤学中的应用
  • 批准号:
    MR/X03657X/1
  • 财政年份:
    2024
  • 资助金额:
    $ 66.05万
  • 项目类别:
    Fellowship
CRII: SHF: A Novel Address Translation Architecture for Virtualized Clouds
CRII:SHF:一种用于虚拟化云的新型地址转换架构
  • 批准号:
    2348066
  • 财政年份:
    2024
  • 资助金额:
    $ 66.05万
  • 项目类别:
    Standard Grant
BIORETS: Convergence Research Experiences for Teachers in Synthetic and Systems Biology to Address Challenges in Food, Health, Energy, and Environment
BIORETS:合成和系统生物学教师的融合研究经验,以应对食品、健康、能源和环境方面的挑战
  • 批准号:
    2341402
  • 财政年份:
    2024
  • 资助金额:
    $ 66.05万
  • 项目类别:
    Standard Grant
The Abundance Project: Enhancing Cultural & Green Inclusion in Social Prescribing in Southwest London to Address Ethnic Inequalities in Mental Health
丰富项目:增强文化
  • 批准号:
    AH/Z505481/1
  • 财政年份:
    2024
  • 资助金额:
    $ 66.05万
  • 项目类别:
    Research Grant
ERAMET - Ecosystem for rapid adoption of modelling and simulation METhods to address regulatory needs in the development of orphan and paediatric medicines
ERAMET - 快速采用建模和模拟方法的生态系统,以满足孤儿药和儿科药物开发中的监管需求
  • 批准号:
    10107647
  • 财政年份:
    2024
  • 资助金额:
    $ 66.05万
  • 项目类别:
    EU-Funded
Ecosystem for rapid adoption of modelling and simulation METhods to address regulatory needs in the development of orphan and paediatric medicines
快速采用建模和模拟方法的生态系统,以满足孤儿药和儿科药物开发中的监管需求
  • 批准号:
    10106221
  • 财政年份:
    2024
  • 资助金额:
    $ 66.05万
  • 项目类别:
    EU-Funded
Recite: Building Research by Communities to Address Inequities through Expression
背诵:社区开展研究,通过表达解决不平等问题
  • 批准号:
    AH/Z505341/1
  • 财政年份:
    2024
  • 资助金额:
    $ 66.05万
  • 项目类别:
    Research Grant
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了