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.
大脑皮层严重依赖于胚胎和早期神经元和神经胶质细胞的平衡产生
产后发育。最近开发的克隆谱系分析揭示了神经干的行为
细胞(NSC)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,
NSCs 神经胶质细胞的形成仍不清楚,并且尚未使用这些新的方法进行系统研究
技术。胶质细胞生成对于正常的神经元功能至关重要,当受到干扰时,可能会导致各种
神经系统疾病。重建神经胶质细胞如何从单个神经干细胞中产生并在神经干细胞中组织
发育过程中的皮层对于理解结构与功能的关系以及它们如何相互关联至关重要
受克隆特异性因子调节。我们建立了基于基因的单细胞谱系追踪
利用 MADM(双标记马赛克分析)小鼠标记发育中皮质中的 NSC 的技术
并开始解决这一知识差距。使用这种方法,我们发现了两个不同的神经胶质细胞群
占据皮质的不同区域及其相关结构海马结构。的目标
拟议的研究是重建、量化和数学建模单独标记的行为
体内 NSC。我们将利用这种标记方法的力量来筛选神经胶质细胞克隆的基因表达
在单细胞分辨率下,这将帮助我们破译组织神经胶质细胞克隆的一般原则
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
皮质中神经胶质克隆生成的基因,这将进一步帮助定义潜在的生物系统
胶质细胞生成的原理。成功完成我们的研究将产生单个 NSC 的综合图谱
及其在各个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
胶质生成、胶质多样性及其再生潜力的定量和计算分析
接近皮质。
产生更广泛影响的潜力
我们了解大脑的重要组成部分——神经胶质细胞——如何发育的方法具有广泛的应用前景。
影响。神经胶质发育的破坏是大脑中一系列病理状况的根源。
因此,了解控制胶质生成的基本原理和细胞机制对于
不仅了解如何通过神经胶质细胞的系统产生来控制健康发育,而且还了解
胶质细胞生成异常如何导致毁灭性的神经发育障碍和脑肿瘤。
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
- 作者:
- 通讯作者:
{{
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 }}
Hooman Troy Ghashghaei其他文献
Hooman Troy Ghashghaei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('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:
相似海外基金
Linkage of HIV amino acid variants to protective host alleles at CHD1L and HLA class I loci in an African population
非洲人群中 HIV 氨基酸变异与 CHD1L 和 HLA I 类基因座的保护性宿主等位基因的关联
- 批准号:
502556 - 财政年份:2024
- 资助金额:
$ 53.2万 - 项目类别:
Olfactory Epithelium Responses to Human APOE Alleles
嗅觉上皮对人类 APOE 等位基因的反应
- 批准号:
10659303 - 财政年份:2023
- 资助金额:
$ 53.2万 - 项目类别:
Deeply analyzing MHC class I-restricted peptide presentation mechanistics across alleles, pathways, and disease coupled with TCR discovery/characterization
深入分析跨等位基因、通路和疾病的 MHC I 类限制性肽呈递机制以及 TCR 发现/表征
- 批准号:
10674405 - 财政年份:2023
- 资助金额:
$ 53.2万 - 项目类别:
An off-the-shelf tumor cell vaccine with HLA-matching alleles for the personalized treatment of advanced solid tumors
具有 HLA 匹配等位基因的现成肿瘤细胞疫苗,用于晚期实体瘤的个性化治疗
- 批准号:
10758772 - 财政年份:2023
- 资助金额:
$ 53.2万 - 项目类别:
Identifying genetic variants that modify the effect size of ApoE alleles on late-onset Alzheimer's disease risk
识别改变 ApoE 等位基因对迟发性阿尔茨海默病风险影响大小的遗传变异
- 批准号:
10676499 - 财政年份:2023
- 资助金额:
$ 53.2万 - 项目类别:
New statistical approaches to mapping the functional impact of HLA alleles in multimodal complex disease datasets
绘制多模式复杂疾病数据集中 HLA 等位基因功能影响的新统计方法
- 批准号:
2748611 - 财政年份:2022
- 资助金额:
$ 53.2万 - 项目类别:
Studentship
Recessive lethal alleles linked to seed abortion and their effect on fruit development in blueberries
与种子败育相关的隐性致死等位基因及其对蓝莓果实发育的影响
- 批准号:
22K05630 - 财政年份:2022
- 资助金额:
$ 53.2万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Genome and epigenome editing of induced pluripotent stem cells for investigating osteoarthritis risk alleles
诱导多能干细胞的基因组和表观基因组编辑用于研究骨关节炎风险等位基因
- 批准号:
10532032 - 财政年份:2022
- 资助金额:
$ 53.2万 - 项目类别:
Investigating the Effect of APOE Alleles on Neuro-Immunity of Human Brain Borders in Normal Aging and Alzheimer's Disease Using Single-Cell Multi-Omics and In Vitro Organoids
使用单细胞多组学和体外类器官研究 APOE 等位基因对正常衰老和阿尔茨海默病中人脑边界神经免疫的影响
- 批准号:
10525070 - 财政年份:2022
- 资助金额:
$ 53.2万 - 项目类别:
Leveraging the Evolutionary History to Improve Identification of Trait-Associated Alleles and Risk Stratification Models in Native Hawaiians
利用进化历史来改进夏威夷原住民性状相关等位基因的识别和风险分层模型
- 批准号:
10689017 - 财政年份:2022
- 资助金额:
$ 53.2万 - 项目类别: