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Molecular Science Core

分子科学核心

基本信息

批准号：
10294400
负责人：
Bosiljka Tasic
金额：
$ 44.05万
依托单位：
ALLEN INSTITUTE
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-01-15 至 2026-12-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10294400
关键词：
ATAC-seq Adult Amygdaloid structure Anatomy Animals Area Automobile Driving Award Axon BRAIN initiative Basal Ganglia Behavioral Brain Brain imaging Cell Nucleus Cells Censuses Cerebellum Chromatin Corpus striatum structure DNA Data Data Analyses Data Set Databases Dependovirus Diffuse Enhancers Fluorescent in Situ Hybridization Gene Expression Genes Genetic Genetic Enhancer Element Genomics Goals Hippocampus (Brain)Institutes Knock-in Label Logic Measures Midbrain structure Modernization Molecular Morphology Mus Neocortex Neurons Organ Pattern Population Process Publishing Reagent Recommendation Regulatory Element Reporter Research Role Science Specificity Standardization Structure Taxonomy Techniques Thalamic Nuclei Thalamic structure Transgenes Transgenic Animals Transgenic Mice Transgenic Organisms Viral Viral Genome Viral Packaging Viral Vector Virus Work base bioinformatics tool candidate marker cell type cellular imaging epigenomics excitatory neuron genetic approach genetic element genomic data improved molecular marker neural circuit public repository recombinase reconstruction single-cell RNA sequencing tomography tool transcription factor transcriptomics two-photon

项目摘要

Summary, Molecular Science Core The thalamus contains excitatory neurons that receive input from diverse areas outside of the thalamus (neocortex, cerebellum, basal ganglia, midbrain, hippocampus) and project to the neocortex. Recent molecular mapping and morphological reconstructions have shown that these thalamocortical (TC) cells are much more diverse than previously thought, both across and within cytoarchitectonically-defined thalamic nuclei. Different TC cells likely receive input from different subcortical structures, and project to different cortical areas and layers. Experimental access to specific TC cell types is essential for elucidating their roles in neural circuit function. Single cell genomics has recently enabled unprecedented definition of cell types at the molecular level and has uncovered numerous marker genes and putative regulatory elements, which can be used to generate genetic tools for access to specific cell populations. For the adult mouse thalamus, we have generated a large-scale single-cell transcriptomics dataset (scRNA-seq) to measure gene expression, and a matching single-nucleus chromatin accessibility dataset (snATAC-seq) to discover putative enhancers. In addition, we are in the process of generating equivalent data for the developing mouse thalamus. These datasets will enable us to select marker genes and enhancers to generate transgenic and viral tools for genetic access to TC types. To refine access to specific TC types, intersectional genetic approaches combining viruses, transgenes, and retrograde labeling will be explored. We will evaluate the completeness of labeling a specific cell population versus specificity at the level of the whole brain, as different levels of specificity / completeness are needed for different experimental purposes. Sparse yet specific labeling is ideal for morphological examination, whereas relatively complete and locally or globally specific labeling is needed for behavioral perturbations. The tools will be used in other research segments (Projects 2, 3, 4) as soon as they become available. Tool characterization will combine standardized Allen Institute pipelines: whole-brain cellular imaging, multiplexed fluorescence in situ hybridization (mFISH), as well as scRNA-seq. DNA constructs, transgenic mice, virus packaging techniques, recommended virus titers, and virus and transgene characterization data will be made available in public repositories.

摘要，分子科学核心