A regulome and transcriptome atlas of fetal and adult human neurogenesis
胎儿和成人神经发生的调节组和转录组图谱
基本信息
- 批准号:10377713
- 负责人:
- 金额:$ 554.85万
- 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:2021-09-20 至 2024-09-19
- 项目状态:已结题
- 来源:
- 关键词:AddressAdultAlzheimer&aposs DiseaseAnatomyAtlasesBRAIN initiativeBindingBiologyBrainBrain DiseasesCell CountCell LineageCell NucleusCellsCensusesChromatinCommunitiesComplementComplexDNADataDefectDevelopmentDevelopmental GeneDiseaseElementsEmbryoEmbryonic DevelopmentEpigenetic ProcessEpitopesEtiologyEvolutionGene ExpressionGenesGenetic TranscriptionGoalsHippocampus (Brain)HumanImageInvestigationLinkLocationMammalsMapsMental DepressionMethodsModelingMusNamesNeurogliaNeuronsNuclearOutcome StudyPatternPlant RootsPopulationPregnancyProcessProliferatingRadialRecording of previous eventsRegulator GenesReportingResearchResolutionResourcesRoleSchizophreniaSmall Nuclear RNASpatial DistributionTechnologyTissuesTranscriptadult neurogenesisbasecell typecomparativecomputing resourcescostdentate gyrusepigenomefetalgenome-widegranule cellhuman dataindexinginnovationmultimodalitynerve stem cellneurodevelopmentneurogenesisneuropsychiatrynonhuman primatenovelnovel therapeuticspostnatalprogramsspatiotemporalstem cellstooltranscription factortranscriptometranscriptomics
项目摘要
PROJECT SUMMARY
Dynamic changes in the spatiotemporal patterning of transcription factor binding on cis-regulatory DNA
elements drives the developmental transition of cell lineages during neurogenesis. In the human brain, neurons
are generated from early embryonic development until early postnatal stages. The main neurogenic region in
the adult brain is the dentate gyrus in the hippocampus. While adult hippocampal neurogenesis has been
confirmed in the majority of mammals, it is unclear if this phenomenon exists in the human brain. Multiple
neuropsychiatric conditions, including depression, schizophrenia and Alzheimer's disease are rooted in
hippocampal defects. Despite
role
Therefore,
the obvious importance of on and its
in neurogenesis, our understanding of the cell diversity and tissue organization is highly incomplete.
a
dentate gyrus neuropsychiatric conditions,
more complete cell census of the dentate gyrus across lifetime will increase our understanding of
the mechanisms underlying fetal, early postnatal and adult neurogenesis, which could have a key role in the
etiology of disease in humans.
tools
chromatin
gyrus
world
computational
resources
The overarching goal of our proposal is to optimize and accelerate the use of scalable technologies and
to perform unbiased, multimodal single-nucleus omics-based assessment of gene expression and
accessibility combined with spatial transcriptomics profiling on tissue sections of human
across stages. In this study, we bring together an interdisciplinary team of
experts anatomy, spatial transcriptomics, neurodevelopment and
biology to create a cell census of the dentate gyrus that will be integrated with existing
from the BRAIN Initiative Cell Census Network and will be made freely available to the scientific
dentate
fetal, early postnatal and adult
in single cell omics, human
community.
analyses
early
embryonic
hippocampal
and
This
 Utilizing this large resource of omics data from the human dentate gyrus, we will perform the following three
that aim to: (1) identify the cell diversity and tissue organization of human dentate gyrus across fetal,
postnatal and adult stages; (2) uncover shared and distinct gene regulatory networks associated with
and adult human hippocampal neurogenesis; and (3) study the evolution conservation of
neurogenesis by performing comparative analysis with mouse and non-human primate single-cell
spatial transcriptomic data that are readily accessible through the BRAIN Initiative Cell Census Network.
innovative research program will, if successful,provide scalable technologies for multimodal and spatial
omics profiling and a developmental and adult cell atlas of cell type diversity in the dentate
gyrus
, which will
serve as a blueprint for studies of human hippocampal neurogenesis, selective vulnerability of cell types in
disease, and the features of brain evolution that differentiates humans from other species.
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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{{ truncateString('Long Cai', 18)}}的其他基金
Dynamics of chromosome organization and chromatin states in single cells
单细胞染色体组织和染色质状态的动力学
- 批准号:10661637 
- 财政年份:2020
- 资助金额:$ 554.85万 
- 项目类别:
Dynamics of chromosome organization and chromatin states in single cells
单细胞染色体组织和染色质状态的动力学
- 批准号:10266830 
- 财政年份:2020
- 资助金额:$ 554.85万 
- 项目类别:
Dynamics of chromosome organization and chromatin states in single cells
单细胞染色体组织和染色质状态的动力学
- 批准号:10456124 
- 财政年份:2020
- 资助金额:$ 554.85万 
- 项目类别:
Spatial genomics single cell analysis of aging brains
衰老大脑的空间基因组学单细胞分析
- 批准号:10196928 
- 财政年份:2019
- 资助金额:$ 554.85万 
- 项目类别:
Spatial genomics single cell analysis of aging brains
衰老大脑的空间基因组学单细胞分析
- 批准号:10410511 
- 财政年份:2019
- 资助金额:$ 554.85万 
- 项目类别:
Spatial genomics single cell analysis of aging brains
衰老大脑的空间基因组学单细胞分析
- 批准号:10020894 
- 财政年份:2019
- 资助金额:$ 554.85万 
- 项目类别:
Spatial genomics single cell analysis of aging brains
衰老大脑的空间基因组学单细胞分析
- 批准号:10618356 
- 财政年份:2019
- 资助金额:$ 554.85万 
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seqFISH core for in situ cell type identification
用于原位细胞类型鉴定的 seqFISH 核心
- 批准号:10438690 
- 财政年份:2018
- 资助金额:$ 554.85万 
- 项目类别:
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