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Epigenomic mapping approaches for cell-type classification in the brain

用于大脑细胞类型分类的表观基因组图谱方法

基本信息

批准号：
9107493
负责人：
M MARGARITA BEHRENS
金额：
$ 91.33万
依托单位：
SALK INSTITUTE FOR BIOLOGICAL STUDIES
依托单位国家：
美国
项目类别：
财政年份：
2014
资助国家：
美国
起止时间：
2014-09-26 至 2017-11-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9107493
关键词：
Adult Age-associated memory impairment Alzheimer&apos s Disease Atlases BRAIN initiative Base of the Brain Behavioral Brain Brain Mapping Brain region Cataloging Catalogs Categories Cells Censuses Characteristics Classification Cortical Cell Layer Cytosine DNA DNA Methylation Data Detection Development Epigenetic Process Equipment and supply inventories Evaluation Foundations Gene Expression Genome Genomics Goals Human In Situ Individual Label Learning Location Maps Memory Methylation Mitotic Modification Molecular Mus Neuroglia Neuronal Plasticity Neurons Parvalbumins Pattern Physiological Population Primary Cell Cultures Primates Process Reading Research Resolution Rodent Schizophrenia Slice Specificity Structure Systems Biology Technology Testing base bisulfite brain cell cell type design epigenomics frontal lobe genome-wide methylome nervous system disorder neurochemistry novel public health relevance

项目摘要

DESCRIPTION (provided by applicant): Understanding the exact cell-type composition in brain regions is fundamental to integrating physiological, behavioral and neurochemical data to systematically understand the brain structure and function. At present, although the major categories of cell-types present in brain have been defined, the different subtypes within these categories, as well as their location and connectivity are far from understood. DNA methylation (mC) is a stable covalent modification that persists in post-mitotic cells throughout their lifetim, defining their cellular identity. It was recently demonstrated that mC patterns in brain are highly dynamic throughout development, and that there are clear differences between the major types of cells i.e., neurons and glia, in the rodent and human cortex. These analyses have been taken a step further and have produced data at the cell-type level that shows that each neuronal type carry specific mC signatures in their genomes that define the population they belong to. These results now open the possibility of producing a catalog of cell-types in brain defined by methylome signatures. This proposal will utilize this cell-type-specific base-resolution methylome data to produce complete maps of cell-types in the rodent brain in situ, and by this means develop a systematic inventory and census of cell types in the brain based on an integrated view of their molecular identity. Based on preliminary results showing clear-cut differences between the methylomes of specific neuronal types, we propose to use cutting edge technology to discover and test specific differentially methylated regions that define, at the molecular level, cell-populations in the frontal cortex of mice. The results obtained will be made publically available, and will serve as foundation to produce a complete genomic census of cell-types in a brain region that can be scaled to the whole brain. If successful, the approach could be ultimately tested in the primate brain. This proposal is thus responsive to RFA MH-14-215 "BRAIN Initiative: Transformative Approaches for Cell-Type Classification in the Brain (U01)".

项目成果

期刊论文数量（4）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Epigenomic Signatures of Neuronal Diversity in the Mammalian Brain.

DOI：
10.1016/j.neuron.2015.05.018
发表时间：
2015-06-17
期刊：
Neuron
影响因子：
16.2
作者：
Mo A;Mukamel EA;Davis FP;Luo C;Henry GL;Picard S;Urich MA;Nery JR;Sejnowski TJ;Lister R;Eddy SR;Ecker JR;Nathans J
通讯作者：
Nathans J

Epigenomic landscapes of retinal rods and cones.

DOI：
10.7554/elife.11613
发表时间：
2016-03-07
期刊：
eLife
影响因子：
7.7
作者：
Mo A;Luo C;Davis FP;Mukamel EA;Henry GL;Nery JR;Urich MA;Picard S;Lister R;Eddy SR;Beer MA;Ecker JR;Nathans J
通讯作者：
Nathans J

Robust single-cell DNA methylome profiling with snmC-seq2.

DOI：
10.1038/s41467-018-06355-2
发表时间：
2018-09-20
期刊：
Nature communications
影响因子：
16.6
作者：
Luo C;Rivkin A;Zhou J;Sandoval JP;Kurihara L;Lucero J;Castanon R;Nery JR;Pinto-Duarte A;Bui B;Fitzpatrick C;O'Connor C;Ruga S;Van Eden ME;Davis DA;Mash DC;Behrens MM;Ecker JR
通讯作者：
Ecker JR