A multimodal atlas of human brain cell types
A multimodal atlas of human brain cell types
批准号:
10165825
负责人:
Ed Lein
金额:
$346.85万
依托单位:
依托单位国家:
美国
项目类别:
财政年份:
2017
资助国家:
美国
项目状态:
已结题
起止时间:
2017-09-20 至 2022-09-30
关键词:
3-DimensionalAdultAffectAmygdaloid structureAnatomyAnimal ModelAtlasesAutopsyBiophysicsBrainBrain DiseasesBrain StemBrain regionCell NucleusCell physiologyCellsCellular MorphologyCellular StructuresCensusesCerebellumClassificationClinicalClinical ResearchCognitionCommunitiesComplexComputing MethodologiesCorpus striatum structureDataData SetDatabasesDevelopmentDiseaseElectrophysiology (science)ElementsEpilepsyExcisionFluorescent in Situ HybridizationFoundationsFunctional disorderGene Expression ProfileGoldHippocampus (Brain)Hodgkin-Huxley modelHumanHypothalamic structureImageIndividualInjuryInstitutesInternationalMapsMeasuresMethodologyMethodsMidbrain structureModalityModelingMolecularMolecular AbnormalityMorphologyMusNeocortexNeuronsNeurosciencesOrganOutcomeOutputPerceptionPhenotypePhysiologicalPhysiologyPreparationPropertyResectedResolutionRoleSamplingScienceSiteSliceSpatial DistributionSpinal CordStandardizationStructureSubcellular AnatomySurvey MethodologySurveysTaxonomyTechniquesThalamic structureTissuesTraumaWorkbasebiophysical modelbrain cellbrain tissuecell typecollaboratorydata centersdata resourcehuman modelhuman tissuemultimodalityneuronal circuitryneurosurgerypatch clamppatch sequencingscale upsingle cell analysissingle moleculesingle-cell RNA sequencingtooltranscriptometranscriptome sequencingtranscriptomicstumor
中文摘要
摘要:
人脑细胞类型的多模态图谱
细胞类型是大脑的构建块,包括形成特定神经元的神经元类型。
负责感知,认知和行动的电路,以及执行其他任务的非神经元元件
对大脑正常功能至关重要。深入了解细胞类型对于了解大脑至关重要
结构和功能,以及疾病和损伤中功能障碍的潜在机制,
通过潜在的遗传异常或通过选择性的
易受侮辱和伤害。尽管细胞类型的重要性显而易见,但我们对它们的理解
多样性、具体属性和离散性是高度不完整的。这在人类大脑中尤其如此,
由于技术的限制,无法获取活体脑组织,再加上其庞大的规模和复杂性,
阻碍了进展;然而,一套新的分子,解剖和生理工具和技术,
现在可以在模型生物和人类的脑组织中工作。标准化和扩大规模
这些技术提供了一个广泛而深刻的理解,
人类大脑的组成部分,以及它们保守而独特的特征。
我们在这里提议,将单细胞领域的世界领导者组成一个跨学科联盟,
转录组学,人类细胞生理学和解剖学,以及神经元建模,以创建一个全面的
人类脑细胞类型图谱作为社区数据资源。这个图谱的基础是一个分子
基于大规模单细胞转录组学的细胞类型分类,结合细胞分类的广泛调查,
通过深入分析新皮层和海马体,
其中可以分析活体神经外科切除中细胞的功能和解剖学特性。
这些分子细胞类型的分布将使用单分子标记在组织切片上作图。
多重荧光原位杂交,以创建不同脑区细胞类型的定量普查。
为了了解这些分子细胞类型的特性,我们将在一个联盟中标准化方法。
的专家在人体切片膜片钳电生理学研究的结构,功能和分子
皮质细胞类型的特性。最后,我们将获得工具来分类细胞类型,执行神经元建模,
了解和预测细胞类型的功能,并比较小鼠和
人类结果将是第一个详细的人类脑细胞类型和发展的地图集。
人类大脑研究的标准化方法,可能会促进基础和临床研究的快速进展。
神经科学
英文摘要
Abstract:
A Multimodal Atlas of Human Brain Cell Types
Cell types are the building blocks of the brain, including the neuron types forming specific neuronal
circuits responsible for perception, cognition and action, and the non-neuronal elements performing other
essential roles for proper brain function. A deep understanding of cell types is essential to understand brain
structure and function, as well as mechanisms underlying dysfunction in disorders and injury, which in general
affect specific cellular components either through underlying genetic abnormalities or through selective
vulnerability to insults and injury. Despite the obvious importance of cell types, our understanding of their
diversity, specific properties and discreteness is highly incomplete. This is particularly true in the human brain,
where technological limitations, lack of access to living brain tissues, and the sheer size and complexity has
hampered progress; however, a new set of molecular, anatomical and physiological tools and techniques are
now available that work in brain tissue both from model organisms and human. Standardization and scale-up
of these techniques offers to dramatically change the field by providing a broad and deep understanding of the
building blocks of the human brain, and their conserved and unique features.
We propose here to bring together an interdisciplinary consortium of world leaders in single cell
transcriptomics, human cellular physiology and anatomy, and neuronal modeling to create a comprehensive
atlas of human brain cell types as a community data resource. The foundation of this atlas is a molecular
classification of cell types based on large-scale single cell transcriptomics, combining a broad survey of cell
types across the entire brain and spinal cord with a deep analysis of the neocortex and hippocampus, regions
in which it is possible to analyze functional and anatomical properties of cells in living neurosurgical resections.
The distribution of these molecular cell types will be mapped on tissue sections using single molecular
multiplex fluorescent in situ hybridization to create a quantitative census of cell types in different brain regions.
To understand the properties of these molecular cell types, we will standardize methods across a consortium
of experts in human slice patch clamp electrophysiology to study the structure, function and molecular
properties of cortical cell types. Finally, we will derive tools to classify cell types, perform neuronal modeling to
understand and predict the function of cell types, and compare cell type properties between mouse and
human. The outcome will be the first detailed atlas of human brain cell types and the development of
standardized methods for human brain study that are likely to catalyze rapid progress in basic and clinical
neuroscience.
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Strong and reliable synaptic communication between pyramidal neurons in adult human cerebral cortex.
DOI:
10.1093/cercor/bhac246
发表时间:
2023-03-10
期刊:
Cerebral cortex (New York, N.Y. : 1991)
影响因子:
--
作者:
[]
通讯作者:
DOI:
10.1038/s41587-022-01455-3
发表时间:
2023-02
期刊:
NATURE BIOTECHNOLOGY
影响因子:
46.9
作者:
[Borm, Lars E., Albiach, Alejandro Mossi, Mannens, Camiel C. A., Janusauskas, Jokubas, Ozgun, Ceren, Fernandez-Garcia, David, Hodge, Rebecca, Castillo, Francisca, Hedin, Charlotte R. H., Villablanca, Eduardo J., Uhlen, Per, Lein, Ed S., Codeluppi, Simone, Linnarsson, Sten]
通讯作者:
Linnarsson, Sten
DOI:
10.1016/j.neuron.2018.10.012
发表时间:
2018-12-05
期刊:
Neuron
影响因子:
16.2
作者:
[Kalmbach BE, Buchin A, Long B, Close J, Nandi A, Miller JA, Bakken TE, Hodge RD, Chong P, de Frates R, Dai K, Maltzer Z, Nicovich PR, Keene CD, Silbergeld DL, Gwinn RP, Cobbs C, Ko AL, Ojemann JG, Koch C, Anastassiou CA, Lein ES, Ting JT]
通讯作者:
Ting JT
DOI:
10.3389/fncel.2018.00181
发表时间:
2018
期刊:
Frontiers in cellular neuroscience
影响因子:
5.3
作者:
[Eyal G, Verhoog MB, Testa-Silva G, Deitcher Y, Benavides-Piccione R, DeFelipe J, de Kock CPJ, Mansvelder HD, Segev I]
通讯作者:
Segev I
DOI:
10.1371/journal.pcbi.1009015
发表时间:
2021-05
期刊:
PLoS computational biology
影响因子:
4.3
作者:
[Moldwin T, Kalmenson M, Segev I]
通讯作者:
Segev I
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Organization and architecture of a Center for cellular resolution analysis of Alzheimer's disease
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Topographic, cell type and molecular pathway characterization ofAlzheimer's disease using single cell transcriptomics and epigenomics
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Organization and architecture of a Center for cellular resolution analysis of Alzheimer's disease
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A multimodal atlas of human brain cell types
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CREATING A DEVELOPMENTAL GENE EXPRESSION ATLAS FOR RHESUS MACAQUE BRAIN
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资助金额:$10.1万
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财政年份:2011
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依托单位:
CREATING A DEVELOPMENTAL GENE EXPRESSION ATLAS FOR RHESUS MACAQUE BRAIN
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批准号:8172625
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资助金额:$15.21万
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依托单位:
Creating a Developmental Gene Expression Atlas for Rhesus Macaque Brain
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批准号:7913438
-
项目类别:
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资助金额:$315.87万
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财政年份:2008
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依托单位:
Creating a Developmental Gene Expression Atlas for Rhesus Macaque Brain
-
批准号:8335351
-
项目类别:
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资助金额:$400.0万
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依托单位:
海外基金