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Spatiotemporal epigenomic and chromosomal architectural cell atlas of developing human brains

人类大脑发育的时空表观基因组和染色体结构细胞图谱

基本信息

批准号：
10689124
负责人：
Chongyuan Luo
金额：
$ 80.81万
依托单位：
UNIVERSITY OF CALIFORNIA LOS ANGELES
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：
2022-09-01 至 2027-06-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10689124
关键词：
10 year old 3-Dimensional 5 year old Adult Alleles Architecture Atlases Automobile Driving BRAIN initiative Biological Assay Birth Brain Brain region Catalogs Cell Lineage Cell Nucleus Cell model Cells Childhood Chromatin Chromatin Loop Classification Complement Computing Methodologies Consensus DNA DNA Methylation DNA methylation profiling Data Data Analyses Data Set Development Developmental Gene Disease Enhancers Epigenetic Process Event Exhibits Gene Expression Gene Expression Profile Gene Expression Regulation Generations Genes Goals Human In Situ Joints Life Link Location Maps Mental disorders Methods Modality Modeling Molecular Molecular Conformation Molecular Profiling Mus Neocortex Nucleic Acid Regulatory Sequences Play Population Predisposition Pregnancy Process Property RNA RNA methylation Regulator Genes Regulatory Element Research Personnel Resources Role Sampling Schizophrenia Sensory Series Specific qualifier value Symptoms Time Tissues Transitional Cell Variant age group autism spectrum disorder brain cell cell type collaboratory combinatorial data management data resource digital epigenomics experience gene interaction gene regulatory network genetic variant genomic data impaired brain development innovation methylome multimodality nano-string neocortical neuropsychiatric disorder nonhuman primate novel postnatal period predictive modeling prenatal programs response single cell technology spatiotemporal stem cells tool transcription factor transcriptome transcriptomics

项目摘要

PROJECT SUMMARY The adult human brain is comprised of numerous cell types exhibiting specific transcriptomic and epigenomic signatures associated with their spatial location, connectivity, and function. Although systematic efforts are underway to characterize cell types in the adult human brain, the transitional cell types and cell states in developing human brains are not fully defined. Our project will use epigenomic and three-dimensional (3D) chromosomal architectural information to classify developmental cell types and identify key regulatory dynamics that may underlie cellular lineage commitment and maturation. Single-cell DNA methylation and chromatin accessibility profiles have been successfully used to de novo identify distinct cell types in developing and adult brains. The single-nucleus joint profiling of DNA methylation and chromatin conformation by sn-m3C-seq provides unique information to identify enhancer-gene looping and provides a resource to link genetic variants associated with neuropsychiatric disorders to genes. Cell types identified with epigenomic information will be integrated with spatial transcriptomic signatures using our innovative single-cell joint profiling method of transcriptome and DNA methylation snmCT-seq. We will determine the spatial and temporal dynamics of developing brain cell types using multiplexed RNA in situ and Digital Spatial Profiling (DSP) assays. We will apply state-of-the-art approaches to integrate multiple data modalities to identify progenitor and transitional cell types, lineage-specific regulatory elements, and enhancer-gene 3D interactions. We will construct cell-type- specific predictive models of cellular trajectory and gene regulation during brain development by integrating transcription factor-gene interaction information with time- and pseudotime-series genomics data. The cell type and regulatory elements catalog of human brain development generated by our project will aid the identification of developing brain cell types involved in neuropsychiatric disorders and regulatory regions susceptible to perturbation by disease-associated variants.

项目总结