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Single-cell multi-omics of cerebellar dysregulation in schizophrenia and bipolar disorder

精神分裂症和双相情感障碍小脑失调的单细胞多组学

基本信息

批准号：
10555339
负责人：
Seth Abrams Ament
金额：
$ 15.45万
依托单位：
UNIVERSITY OF MARYLAND BALTIMORE
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：
2022-02-01 至 2024-01-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10555339
关键词：
Address Anatomy Animal Model Area Autopsy Behavioral Biological Assay Bipolar Disorder Brain Brain imaging Brain region Cell Nucleus Cells Cellular Morphology Cerebellar vermis structure Cerebellum Chromatin Cognition Cytoplasmic Granules Data Data Set Disease Enhancers Family Fiber Gene Expression Gene Expression Profiling Gene Expression Regulation Genes Genetic Genetic Transcription Genomics Individual Knowledge Link Maps Mental disorders Modeling Neocortex Neurocognitive Neuroglia Neurons Neurosciences Patients Psychiatric Diagnosis Public Health Quantitative Trait Loci Regulator Genes Resources Role Schizophrenia Structure Synapses System Tissue Sample Transposase XCL1 gene brain tissue cell type differential expression effective therapy emotion regulation epigenomics gene network gene regulatory network gene repression genetic analysis genetic approach genome wide association study imaging study insight multiple omics neocortical network models neural circuit neurobiological mechanism neuropsychiatric disorder new therapeutic target novel therapeutics promoter public health relevance single nucleus RNA-sequencing trait transcriptome transcriptomics

项目摘要

Project Summary Neuropsychiatric disorders such as schizophrenia (SCZ) and bipolar disorder (BD) represent a substantial public health burden. The identification of disease-associated genes and gene networks has long been viewed as one of the most promising paths toward new therapies. In recent years, substantial progress has been made toward the discovery of these disease-associated genes through transcriptomic and epigenomic studies of post-mortem brain tissue. However, while SCZ and BD are associated with structural and functional changes in multiple cortical and sub-cortical brain regions, large-scale genomic studies have focused almost exclusively on a small number of neocortical areas. Several lines of evidence support an important role for the cerebellum in SCZ and BD, including results from brain imaging studies, anatomical studies, and gene expression profiling, and studies in animal models confirm important roles for the cerebellum in the regulation of emotional states and cognition. Here, we will perform single-nucleus RNA sequencing and single-nucleus chromatin accessibility assays to characterize associations of SCZ and BD with cell type-specific transcriptomic and epigenomic changes in the cerebellum (n=25 each for SCZ, BD, and non-diseased controls). Using these data, we will perform systems genetics analyses to predict “convergent neuroscience” mechanisms in the cerebellum, linking SNPs to genes to cell types to brain structure and function to psychiatric diagnoses.

项目总结