Developing cell type-specific enhancers and connectivity mapping pipelines for marmosets
开发狨猴的细胞类型特异性增强剂和连接映射管道
基本信息
- 批准号:10478105
- 负责人:
- 金额:$ 145.51万
- 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 2024-06-30
- 项目状态:已结题
- 来源:
- 关键词:ATAC-seqAffectAntibodiesAreaAtlasesAutomobile DrivingBar CodesBrainBrain DiseasesCRISPR/Cas technologyCallithrixCallithrix jacchus jacchusCell NucleusCellsCercopithecidaeChromatinCommunitiesCorpus striatum structureDNA SequenceDataData AnalyticsData SetDevelopmentDisease modelEnhancersGene Expression ProfileGenesGeneticGenetic EngineeringGenetic Enhancer ElementGenetic ModelsGenetic ResearchHumanHuman GeneticsInjectionsLate-Onset DisorderLongevityMacacaMapsMediatingMethodsModelingMusNeuronsNeurosciencesNeurosciences ResearchOutputPhasePhylogenetic AnalysisPhysiologyPrimatesReproductionRodentRodent ModelSmall Nuclear RNASpecificityStructureStudy modelsTestingThalamic structureVirusWorkanalytical toolbrain cellcell typecognitive functioncomparativecomputational pipelinescostimprovedin vivomultimodalitynonhuman primatenovelpromotersingle-cell RNA sequencingtooltranscriptome sequencingtranscriptomics
项目摘要
PROJECT SUMMARY
Although genetic tools have dramatically advanced our understanding of brain function, they have
largely been confined to mice. While mice are essential models for many areas of neuroscience, there are also
many aspects of higher brain function that cannot be adequately modeled in rodents. Similarly, many brain
disorders affect higher cognitive functions that have no clear parallels in rodents. Furthermore, recent large-
scale single cell transcriptomic analyses have revealed many neuron types, connections and gene expression
patterns that are unique to primates. Thus, there is an urgent need for new genetic models that have brain
structure and function closer to humans. Non-human primates (NHP) are much more closely related to humans
than are rodents, and this is reflected in their brain development, structure and physiology. Hence, it is
increasingly recognized that they provide an attractive model to study higher brain function and brain disorders.
A promising emerging NHP model is the common marmoset, a small new world primate that has many
advantages for neuroscience and genetic research. However, lack of tools with cell type specificity has been a
major obstacle in advancing structural and functional studies in NHP. With the combined single cell RNA-seq
and single cell ATAC-seq, it is now possible to nominate short cell type-specific enhancer sequences. If
validated, these enhancers will provide an effective tool to map connectivity and interrogate function using
virus mediated expression. The difficulty lies in the identification of functional enhancers from the hundreds or
thousands of nominated potential enhancer sequences in NHP. Here we propose (1) to use a novel high
throughput in vivo approach to identify functional enhancers, and (2) to establish a whole-brain circuit mapping
pipeline for use striatal circuitry to validate our approach for cell type-specific connectivity mapping in
marmosets. When completed, these studies will provide much needed essential tools, methods and
computational pipelines for cell type-specific mapping and functional interrogation of the marmoset brain in
healthy and disease models.
项目摘要
尽管遗传工具极大地促进了我们对大脑功能的理解,
主要局限于小鼠。虽然小鼠是神经科学许多领域的基本模型,但也有一些研究。
高级大脑功能的许多方面无法在啮齿动物中充分建模。同样,许多大脑
这些疾病影响高级认知功能,在啮齿类动物中没有明显的相似之处。此外,近期大...
大规模的单细胞转录组学分析揭示了许多神经元类型、连接和基因表达
灵长类动物特有的模式因此,迫切需要新的遗传模型,
结构和功能更接近人类。非人类灵长类动物(NHP)与人类的关系更为密切
比啮齿类动物更好,这反映在它们的大脑发育,结构和生理上。因此,它是
越来越多的人认识到,它们为研究高级脑功能和脑疾病提供了一个有吸引力的模型。
一个有希望的新兴NHP模型是普通的绒猴,一种新世界的小型灵长类动物,
神经科学和遗传学研究的优势。然而,缺乏具有细胞类型特异性的工具一直是一个难题。
推进NHP结构和功能研究的主要障碍。使用组合的单细胞RNA-seq
和单细胞ATAC-seq,现在可以指定短细胞类型特异性增强子序列。如果
经验证,这些增强子将提供一种有效的工具来映射连接和询问功能,
病毒介导的表达。困难在于从数百种或更多种功能增强子中识别出来
NHP中数千个提名的潜在增强子序列。在这里,我们建议(1)使用一种新的高
通过体内方法鉴定功能增强子,以及(2)建立全脑回路映射
管道使用纹状体电路,以验证我们的方法,细胞类型特异性连接映射,
绒猴这些研究完成后,将提供急需的基本工具、方法和
用于绒猴脑细胞类型特异性映射和功能询问的计算管道,
健康和疾病模型。
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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Guoping Feng其他文献
Guoping Feng的其他文献
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{{ truncateString('Guoping Feng', 18)}}的其他基金
BRAIN CONNECTS: Comprehensive regional projection map of marmoset with single axon and cell type resolution
大脑连接:具有单轴突和细胞类型分辨率的狨猴综合区域投影图
- 批准号:
10664170 - 财政年份:2023
- 资助金额:
$ 145.51万 - 项目类别:
Functional dissection of thalamocortical interactions through genetically-defined TRN subnetworks
通过基因定义的 TRN 子网络对丘脑皮质相互作用进行功能剖析
- 批准号:
10622039 - 财政年份:2022
- 资助金额:
$ 145.51万 - 项目类别:
A Genetic Engineering Toolbox for Marmosets (GETMarm): Development and optimization of genome editing and assisted reproduction techniques for marmoset models
狨猴基因工程工具箱 (GETMarm):狨猴模型基因组编辑和辅助生殖技术的开发和优化
- 批准号:
10624895 - 财政年份:2021
- 资助金额:
$ 145.51万 - 项目类别:
Developing cell type-specific enhancers and connectivity mapping pipelines for marmosets
开发狨猴的细胞类型特异性增强剂和连接映射管道
- 批准号:
10653998 - 财政年份:2021
- 资助金额:
$ 145.51万 - 项目类别:
A Genetic Engineering Toolbox for Marmosets (GETMarm): Development and optimization of genome editing and assisted reproduction techniques for marmoset models
狨猴基因工程工具箱 (GETMarm):狨猴模型基因组编辑和辅助生殖技术的开发和优化
- 批准号:
10286437 - 财政年份:2021
- 资助金额:
$ 145.51万 - 项目类别:
A Genetic Engineering Toolbox for Marmosets (GETMarm): Development and optimization of genome editing and assisted reproduction techniques for marmoset models
狨猴基因工程工具箱 (GETMarm):狨猴模型基因组编辑和辅助生殖技术的开发和优化
- 批准号:
10459550 - 财政年份:2021
- 资助金额:
$ 145.51万 - 项目类别:
A Genetic Engineering Toolbox for Marmosets (GETMarm): Development and optimization of genome editing and assisted reproduction techniques for marmoset models
狨猴基因工程工具箱 (GETMarm):狨猴模型基因组编辑和辅助生殖技术的开发和优化
- 批准号:
10832288 - 财政年份:2021
- 资助金额:
$ 145.51万 - 项目类别:
Developing cell type-specific enhancers and connectivity mapping pipelines for marmosets
开发狨猴的细胞类型特异性增强剂和连接映射管道
- 批准号:
10271630 - 财政年份:2021
- 资助金额:
$ 145.51万 - 项目类别:
Functional dissection of thalamocortical interactions through genetically-defined TRN subnetworks
通过基因定义的 TRN 子网络对丘脑皮质相互作用进行功能剖析
- 批准号:
10408808 - 财政年份:2019
- 资助金额:
$ 145.51万 - 项目类别:
Functional dissection of thalamocortical interactions through genetically-defined TRN subnetworks
通过基因定义的 TRN 子网络对丘脑皮质相互作用进行功能剖析
- 批准号:
10198061 - 财政年份:2019
- 资助金额:
$ 145.51万 - 项目类别:
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