Astrocyte Transcriptional Dependencies in Brain Circuits
脑回路中星形胶质细胞的转录依赖性
基本信息
- 批准号:10665221
- 负责人:
- 金额:$ 76.53万
- 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:2023-05-15 至 2031-04-30
- 项目状态:未结题
- 来源:
- 关键词:AdultAlzheimer&aposs DiseaseAstrocytesBrainCellsDependenceDevelopmentDiseaseExhibitsFamilyFamily StudyFunctional disorderGenesGenetic TranscriptionHippocampusKnowledgeLinkMapsMolecularNFIA geneNeurodegenerative DisordersNeuronsPathogenesisPhysiologicalPlayPropertyProteomicsRenaissanceRoleaging brainepigenomicsmembermouse modelnervous system disordernuclear factor 1olfactory bulbtranscription factortranscriptomics
项目摘要
Project Summary
Over the past twenty years our knowledge of astrocytes has undergone a renaissance highlighted by the
identification of dynamic physiological activities, key roles in circuit function, and diverse molecular properties.
Central to the physiological activities of every cell are transcription factors (TFs), yet roles for TFs in mature
astrocyte function and associated circuits in the brain have remained relatively undefined. Our molecular
studies on astrocyte diversity highlighted the expression of developmental TFs in mature astrocytes, in the
adult brain. Among these TFs are members of the Nuclear Factor I (NFI)- and Sox- family, which play essential
roles in early astrocyte development and continue to be expressed in a vast majority of mature astrocytes
throughout the adult brain. Despite exhibiting universal expression in astrocytes across all regions, we found
that NFIA and Sox9 exhibit region specific roles in mature astrocytes, where hippocampal astrocytes require
NFIA to maintain their functional integrity, while olfactory bulb astrocytes require Sox9.
Our finding that astrocytes exhibit region specific transcriptional dependencies, where at given TF is
absolutely essential for function in one region, but is dispensable in other regions, serves as the foundational
observation for this R35 application. We will use other NFI- and Sox- family TF members that are universally
expressed in astrocytes to map region-specific transcriptional dependencies across the developing, adult, and
aging brain. Our analysis will be comprehensive, spanning core astrocyte functions, interactions with neurons,
and circuit-level activities. We posit that these region-specific transcriptional dependencies for astrocyte
function will provide an entry point for understanding how astrocyte diversity is encoded. Therefore, we will use
a host of transcriptomic, epigenomic, and proteomic approaches to uncover how these regional-specific TF
functions are conferred, while functionalizing roles for key downstream target genes. Finally, astrocyte
dysfunction is associated with a host of neurodegenerative diseases, including Alzheimer’s Disease. Here, we
will apply our findings and new mouse models to AD, seeking to uncover how these core features of astrocyte
TF function contribute to AD disease pathogenesis.
项目总结
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)
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Benjamin Deneen其他文献
Benjamin Deneen的其他文献
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{{ truncateString('Benjamin Deneen', 18)}}的其他基金
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癌症新形态驱动因素的系统表征和靶向
- 批准号:
10717973 - 财政年份:2023
- 资助金额:
$ 76.53万 - 项目类别:
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- 批准号:
10736436 - 财政年份:2023
- 资助金额:
$ 76.53万 - 项目类别:
Defining Astrocyte Engram Ensembles During Memory Formation
定义记忆形成过程中的星形胶质细胞印迹整体
- 批准号:
10722056 - 财政年份:2023
- 资助金额:
$ 76.53万 - 项目类别:
Cellular and Molecular Mechanisms of GBM Infiltration
GBM 浸润的细胞和分子机制
- 批准号:
10583559 - 财政年份:2022
- 资助金额:
$ 76.53万 - 项目类别:
Cellular and Molecular Mechanisms of GBM Infiltration
GBM 浸润的细胞和分子机制
- 批准号:
10383061 - 财政年份:2022
- 资助金额:
$ 76.53万 - 项目类别:
MOLECULAR AND CELLULAR CONTROL OF INJURY-INDUCED ASTROGENESIS
损伤引起的星形细胞生成的分子和细胞控制
- 批准号:
10335708 - 财政年份:2021
- 资助金额:
$ 76.53万 - 项目类别:
Defining Roles for Astrocyte Subpopulations in the Aging Brain
定义星形胶质细胞亚群在衰老大脑中的作用
- 批准号:
10192033 - 财政年份:2021
- 资助金额:
$ 76.53万 - 项目类别:
Defining Roles for Astrocyte Subpopulations in the Aging Brain
定义星形胶质细胞亚群在衰老大脑中的作用
- 批准号:
10581539 - 财政年份:2021
- 资助金额:
$ 76.53万 - 项目类别:
Defining Roles for Astrocyte Subpopulations in the Aging Brain
定义星形胶质细胞亚群在衰老大脑中的作用
- 批准号:
10390425 - 财政年份:2021
- 资助金额:
$ 76.53万 - 项目类别:
Defining Roles for Astrocyte Subpopulations in the Aging Brain
定义星形胶质细胞亚群在衰老大脑中的作用
- 批准号:
10708356 - 财政年份:2021
- 资助金额:
$ 76.53万 - 项目类别:














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