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
基本信息
- 批准号:10192033
- 负责人:
- 金额:$ 32.8万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2021
- 资助国家:美国
- 起止时间:2021-04-15 至 2026-02-28
- 项目状态:未结题
- 来源:
- 关键词:AddressAffectAgingAllelesAlzheimer&aposs DiseaseAnatomyAreaAstrocytesBacterial Artificial ChromosomesBlood - brain barrier anatomyBrainBrain regionCell surfaceChIP-seqCoupledDataDiseaseEvolutionExhibitsGenesGeneticGenetic TranscriptionGoalsHippocampus (Brain)Knockout MiceLabelLinkMetabolicMolecularMolecular ProfilingMorphologyMusNatureNeurodegenerative DisordersNeurogliaNeuronsNeurosciencesPathologicPhysiologicalPhysiologyPlayPopulationPropertyReporterRoleage relatedaging brainbasegenetic approachin vivomouse modelnervous system disorderneurotransmissionnovelolfactory bulbprospectiveresponse to injurysingle-cell RNA sequencingsynaptogenesistranscription factor
项目摘要
Summary
Astrocytes are the most abundant type of glial cell in the CNS and play vital roles in all
facets of brain physiology. Recent studies from our lab identified five molecularly and
functionally distinct astrocyte subpopulations in the brain. One of these subpopulations is
specifically labeled by the cell surface maker CD51 and is endowed with enhanced
synaptogenic function, leading us to hypothesize that CD51+ astrocytes play an important role
in functioning brain circuits. To determine how CD51+ astrocytes contribute to circuit function,
we created a CD51-FLP mouse line that allows us selectively label and manipulate this
population of astrocytes in the brain. To decipher the mechanisms that regulate CD51+
astrocytes, we found that the transcription factor Sox9 is enriched in this subpopulation.
Preliminary studies in a newly generated mouse line that specifically eliminates Sox9 in
astrocytes revealed that this transcription factor selectively regulates astrocyte morphology and
circuit function in the hippocampus and olfactory bulb in an aging-dependent manner. Together,
these new mouse lines will enable us to uncover how CD51+ astrocytes regulate brain circuits
and reveal novel roles for Sox9 in controlling astrocyte diversity and function during aging.
Based on the strength of these preliminary observations, we propose the following
specific aims. In specific aim 1, we will define the anatomical, morphological and physiological
properties of CD51+ and CD51- astrocytes in the aging brain and decipher how they contribute
to circuit function in the hippocampus and olfactory bulb. In specific aim 2, we will use our
astrocyte-specific Sox9 knockout mouse to decipher how it regulates astrocyte function in the
aging brain and how these changes in astrocytes impact circuit function in the hippocampus and
olfactory bulb. In specific aim 3 we will determine how Sox9 regulates astrocyte diversity during
aging and integrate our findings with Sox9 ChIP-Seq to decipher Sox9 target gene networks.
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
Astrocyte Transcriptional Dependencies in Brain Circuits
脑回路中星形胶质细胞的转录依赖性
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10665221 - 财政年份:2023
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Systematic Characterization and Targeting of Neomorphic Drivers in Cancer
癌症新形态驱动因素的系统表征和靶向
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10717973 - 财政年份:2023
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Transcriptional Regulation in ZFTA-RELA Ependymoma
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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
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10722056 - 财政年份:2023
- 资助金额:
$ 32.8万 - 项目类别:
Cellular and Molecular Mechanisms of GBM Infiltration
GBM 浸润的细胞和分子机制
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10583559 - 财政年份:2022
- 资助金额:
$ 32.8万 - 项目类别:
Cellular and Molecular Mechanisms of GBM Infiltration
GBM 浸润的细胞和分子机制
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10383061 - 财政年份:2022
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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:
$ 32.8万 - 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:
$ 32.8万 - 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:
$ 32.8万 - 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:
$ 32.8万 - 项目类别:
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