Clonal analysis of gliogenesis in the cerebral cortex
大脑皮层胶质生成的克隆分析
基本信息
- 批准号:10260078
- 负责人:
- 金额:$ 53.2万
- 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:2021-09-01 至 2024-08-31
- 项目状态:已结题
- 来源:
- 关键词:AddressAllelesAlzheimer&aposs DiseaseAreaBehaviorBioinformaticsBiologicalBiologyBrainBrain NeoplasmsCandidate Disease GeneCell CycleCell LineageCellsCerebral cortexColorComputer AnalysisDataDevelopmentDiseaseDorsalDoseEmbryoEpidermal Growth Factor ReceptorEquilibriumEventExperimental ModelsGene ExpressionGenerationsGenesGeneticGenotypeGliomaGliosisGoalsHippocampal FormationHippocampus (Brain)HomeostasisIndividualInjuryIonsKnowledgeLabelLeadLifeMapsMethodologyMethodsMitotic RecombinationModelingMosaicismMultiple SclerosisMusNeocortexNeurodevelopmental DisorderNeurogliaNeuronsPathologicPatternPlant RootsPopulationPopulation SizesProductionProsencephalonProteinsRegulationResearchResearch ProposalsResolutionRoleSiblingsSpinal cord injuryStrokeStructureStructure-Activity RelationshipTechniquesTestingTimeTreesanalytical methodbasebiological systemscell behaviorcell growthcell typedosagefallsglial cell developmentgliogenesisimprovedin vivomathematical modelmultimodalitynerve stem cellnervous system disorderneurogenesisnew technologynovelolfactory bulbpostnatalpostnatal developmentprogenitorregeneration potentialregenerative approachregional differenceresponseresponse to brain injuryresponse to injurysingle-cell RNA sequencingstem cell expansiontissue regeneration
项目摘要
The cerebral cortex critically relies on balanced production of neurons and glia during embryonic and early
postnatal development. Recently developed clonal lineage analysis has revealed the behavior of neural stem
cells (NSCs) giving rise to neurons in the cerebral cortex with unprecedented single-cell resolution. However,
the formation of glia by NSCs remains unclear and has yet to be systematically investigated using these new
technologies. Gliogenesis is critical for proper neuronal functions and when disrupted, it can result in various
neurological diseases. Reconstructing how glia are generated from individual NSCs and organized in the
cortex during development is essential to understand the structure-function relationships and how they can be
modulated by clone-specific factors. We have established a genetically-based single-cell lineage tracing
technique utilizing MADM (Mosaic Analysis with Double Markers) mice to label NSCs in the developing cortex
and begin to address this knowledge gap. Using this method we have found two distinct populations of glia that
occupy different territories of the cortex and its related structure the hippocampal formation. The goal of the
proposed research is to reconstruct, quantify, and mathematically model the behavior of individually labeled
NSCs in vivo. We will use the power of this labeling method to also screen for gene expression of glial clones
at single cell resolution, which all together will help us decipher the general principles organizing glial clones in
the cortex, and define how clonal siblings interact with each other. We will test the role of some of the identified
genes in generation of glial clones in the cortex, which will further help define the biological system underlying
principles of gliogenesis. Successful completion of our study will result in a comprehensive map of single NSCs
and their glial progeny in various cortical regions. Our approach will also establish a platform for detailed
quantitative and computational analysis of gliogenesis, glial diversity, and their potential for regenerative
approaches in the cortex.
Potential for Broader Impact
Our approaches to understand how important constituents of the brain, the glial cells, develop have wide
implications. Disruption of glial development is the root of a range of pathological conditions in the brain.
Therefore, understanding the basic principles and cellular mechanisms that control gliogenesis is critical to
appreciate not only how healthy development may be controlled by systematic production of glial cells, but also
how abnormalities in gliogenesis may lead to devastating neurodevelopmental disorders and brain tumors.
大脑皮层在胚胎和早期非常依赖于神经元和神经胶质细胞的平衡产生。
后天发育。最近发展起来的克隆谱系分析揭示了神经干细胞的行为
细胞(NSCs)以前所未有的单细胞分辨率在大脑皮层中产生神经元。然而,
神经干细胞形成神经胶质细胞的机制尚不清楚,尚未利用这些新技术进行系统研究。
技术。胶质形成对正常的神经元功能至关重要,当受到干扰时,它可以导致各种
神经系统疾病。重建神经胶质细胞是如何从单个神经干细胞产生并在
发育过程中的皮质对于理解结构-功能关系以及它们是如何
受克隆特有因子的调节。我们已经建立了一种基于基因的单细胞谱系追踪
利用MADM小鼠标记发育中皮质神经干细胞的技术
并开始解决这一知识鸿沟。使用这种方法,我们发现了两种不同的胶质细胞群体
占据不同区域的皮质及其相关结构,即海马体结构。的目标是
建议的研究是重建、量化和数学建模个别标记的行为
体内的神经干细胞。我们将利用这种标记方法的力量来筛选神经胶质克隆的基因表达
在单细胞分辨率下,所有这些都将帮助我们破译组织神经胶质克隆的一般原理
大脑皮层,并定义克隆兄弟姐妹如何相互作用。我们将测试一些已确定的角色
基因在皮质神经胶质克隆的生成中的作用,这将进一步帮助定义潜在的生物系统
神经胶质发生的原理。成功完成我们的研究将产生一张关于单个NSC的全面地图
以及它们在不同皮质区域的神经胶质后代。我们的方法还将建立一个详细的平台
神经胶质发生、神经胶质多样性及其再生潜能的定量和计算分析
进入大脑皮层。
潜在的更广泛的影响
我们了解大脑的重要组成部分--神经胶质细胞如何发育的方法很广泛。
这意味着什么。神经胶质发育障碍是大脑中一系列病理性疾病的根源。
因此,了解控制胶质形成的基本原理和细胞机制对于
不仅要了解胶质细胞的系统性生产如何控制健康的发育,而且要了解
胶质形成的异常如何导致毁灭性的神经发育障碍和脑瘤。
项目成果
期刊论文数量(1)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
COMBINe enables automated detection and classification of neurons and astrocytes in tissue-cleared mouse brains.
- DOI:10.1016/j.crmeth.2023.100454
- 发表时间:2023-04-24
- 期刊:
- 影响因子:0
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Hooman Troy Ghashghaei其他文献
Hooman Troy Ghashghaei的其他文献
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{{ truncateString('Hooman Troy Ghashghaei', 18)}}的其他基金
High Throughput Clonal Analyses of Gliogenesis in Neocortical and Paleocortical areas of the Mouse Brain
小鼠大脑新皮质和古皮质区域胶质生成的高通量克隆分析
- 批准号:
10536298 - 财政年份:2022
- 资助金额:
$ 53.2万 - 项目类别:
Mechanisms of cytokinesis and delamination in the cerebral cortices
大脑皮质胞质分裂和分层的机制
- 批准号:
9791777 - 财政年份:2014
- 资助金额:
$ 53.2万 - 项目类别:
Mechanisms of cytokinesis and delamination in the cerebral cortices
大脑皮质胞质分裂和分层的机制
- 批准号:
9134875 - 财政年份:2014
- 资助金额:
$ 53.2万 - 项目类别:
Mechanisms of cytokinesis and delamination in the cerebral cortices
大脑皮质胞质分裂和分层的机制
- 批准号:
9343067 - 财政年份:2014
- 资助金额:
$ 53.2万 - 项目类别:
Transcriptional regulation of aging in the adult neural stem cell niche
成体神经干细胞生态位衰老的转录调控
- 批准号:
8234492 - 财政年份:2010
- 资助金额:
$ 53.2万 - 项目类别:
Development and Application of New Ionization Methods for Biological Mass Spectro
生物质谱新型电离方法的开发与应用
- 批准号:
7981584 - 财政年份:2010
- 资助金额:
$ 53.2万 - 项目类别:
Transcriptional regulation of aging in the adult neural stem cell niche
成体神经干细胞生态位衰老的转录调控
- 批准号:
8197309 - 财政年份:2010
- 资助金额:
$ 53.2万 - 项目类别:
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