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Association of gene expression and brain connectivity in human cerebral cortex development and adulthood

人类大脑皮层发育和成年期基因表达与大脑连接的关联

基本信息

批准号：
10449504
负责人：
Hao Huang
金额：
$ 46.85万
依托单位：
CHILDREN'S HOSP OF PHILADELPHIA
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 2026-06-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10449504
关键词：
Adolescence Adult Age Anatomy Area Atlases Axon Brain Brain region Candidate Disease Gene Cell Nucleus Cells Cerebral cortex Childhood Cognition Communities Complement Data Data Set Development Diffusion Magnetic Resonance Imaging Gene Expression Gene Expression Profile Generations Genes Genetic Transcription Genotype Human Human Development Individual Longevity Magnetic Resonance Imaging Maps Mediating Modality Molecular Mus Neocortex Neurons Pattern Plant Roots Prefrontal Cortex Process Research Resolution Resources Schizophrenia Science Small Nuclear RNA Source Specimen Techniques Third Pregnancy Trimester Time Tissues Translating autism spectrum disorder base cell type computerized tools connectome connectome data data harmonization early childhood frontier functional genomics genomic data infancy innovation insight neocortical neural patterning neuropsychiatric disorder next generation novel postnatal postnatal development postnatal human postnatal period prenatal relating to nervous system spatiotemporal tool transcriptome transcriptome sequencing transcriptomics web portal

项目摘要

ABSTRACT The cell-to-cell connections that comprise the functional circuitry and global network organization of the human brain have at their root precise spatiotemporal patterns of gene expression that differentiate brain regions, cell types, and developmental periods. Recent discoveries have revealed highly dynamic spatiotemporal patterns of gene expression throughout development and in several regions of the brain, but elucidating the neural connectome – the comprehensive map of all neural connections – at multiple ages of human development has, until recently, not been practical. Consequently, although we now have a strong understanding of transcriptional reorganizations in the developing and adult human brain, how these dynamics mediate other key phenomena essential for brain function, such as neural connectivity, is not well understood. As region-specific disruptions to neural connectivity may underlie neuropsychiatric disorders including schizophrenia and autism spectrum disorder, the association of transcriptome information with connectivity is a critical next frontier for analysis. We therefore propose to integrate human brain connectome based on neural MRI and transcriptome data collected across multiple timepoints in human postnatal development with unprecedented spatial resolution to implicate candidate genes, gene expression modules, brain regions, developmental periods, and connectivity patterns with human brain development. To accomplish this, we will develop a high-resolution connectome atlas established with unique existing developmental and adult data as well as next-generation connectome data from early and late childhood being acquired with other sources. This atlas will be paired with transcriptomic atlas from the postnatal human neocortex consisting of 25 neocortical areas and will be integrated with publicly available, less comprehensive transcriptomic data generated at the level of the single cell. Finally, we will validate gene expression patterns and the associations we reveal, and freely disseminate atlases and datasets through an integrated web portal.

摘要