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A regulome and transcriptome atlas of fetal and adult human neurogenesis

胎儿和成人神经发生的调节组和转录组图谱

基本信息

批准号：
10377713
负责人：
Long Cai
金额：
$ 554.85万
依托单位：
ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-09-20 至 2024-09-19
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10377713
关键词：
Address Adult Alzheimer&apos s Disease Anatomy Atlases BRAIN initiative Binding Biology Brain Brain Diseases Cell Count Cell Lineage Cell Nucleus Cells Censuses Chromatin Communities Complement Complex DNA Data Defect Development Developmental Gene Disease Elements Embryo Embryonic Development Epigenetic Process Epitopes Etiology Evolution Gene Expression Genes Genetic Transcription Goals Hippocampus (Brain)Human Image Investigation Link Location Mammals Maps Mental Depression Methods Modeling Mus Names Neuroglia Neurons Nuclear Outcome Study Pattern Plant Roots Population Pregnancy Process Proliferating Radial Recording of previous events Regulator Genes Reporting Research Resolution Resources Role Schizophrenia Small Nuclear RNA Spatial Distribution Technology Tissues Transcript adult neurogenesis base cell type comparative computing resources cost dentate gyrus epigenome fetal genome-wide granule cell human data indexing innovation multimodality nerve stem cell neurodevelopment neurogenesis neuropsychiatry nonhuman primate novel novel therapeutics postnatal programs spatiotemporal stem cells tool transcription factor transcriptome transcriptomics

项目摘要

PROJECT SUMMARY Dynamic changes in the spatiotemporal patterning of transcription factor binding on cis-regulatory DNA elements drives the developmental transition of cell lineages during neurogenesis. In the human brain, neurons are generated from early embryonic development until early postnatal stages. The main neurogenic region in the adult brain is the dentate gyrus in the hippocampus. While adult hippocampal neurogenesis has been confirmed in the majority of mammals, it is unclear if this phenomenon exists in the human brain. Multiple neuropsychiatric conditions, including depression, schizophrenia and Alzheimer's disease are rooted in hippocampal defects. Despite role Therefore, the obvious importance of on and its in neurogenesis, our understanding of the cell diversity and tissue organization is highly incomplete. a dentate gyrus neuropsychiatric conditions, more complete cell census of the dentate gyrus across lifetime will increase our understanding of the mechanisms underlying fetal, early postnatal and adult neurogenesis, which could have a key role in the etiology of disease in humans. tools chromatin gyrus world computational resources The overarching goal of our proposal is to optimize and accelerate the use of scalable technologies and to perform unbiased, multimodal single-nucleus omics-based assessment of gene expression and accessibility combined with spatial transcriptomics profiling on tissue sections of human across stages. In this study, we bring together an interdisciplinary team of experts anatomy, spatial transcriptomics, neurodevelopment and biology to create a cell census of the dentate gyrus that will be integrated with existing from the BRAIN Initiative Cell Census Network and will be made freely available to the scientific dentate fetal, early postnatal and adult in single cell omics, human community. analyses early embryonic hippocampal and This Utilizing this large resource of omics data from the human dentate gyrus, we will perform the following three that aim to: (1) identify the cell diversity and tissue organization of human dentate gyrus across fetal, postnatal and adult stages; (2) uncover shared and distinct gene regulatory networks associated with and adult human hippocampal neurogenesis; and (3) study the evolution conservation of neurogenesis by performing comparative analysis with mouse and non-human primate single-cell spatial transcriptomic data that are readily accessible through the BRAIN Initiative Cell Census Network. innovative research program will, if successful,provide scalable technologies for multimodal and spatial omics profiling and a developmental and adult cell atlas of cell type diversity in the dentate gyrus , which will serve as a blueprint for studies of human hippocampal neurogenesis, selective vulnerability of cell types in disease, and the features of brain evolution that differentiates humans from other species.

项目总结