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Single-Cell Transcriptomic Analysis of Human Retina

人类视网膜的单细胞转录组分析

基本信息

批准号：
10159930
负责人：
Mingyao Li
金额：
$ 53.49万
依托单位：
UNIVERSITY OF PENNSYLVANIA
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-05-01 至 2023-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10159930
关键词：
Address Adult Affect Age related macular degeneration Alabama Alleles Alzheimer&apos s Disease Anatomy Animal Model Atlases Automobile Driving Autopsy Back Biology Blindness Brain Cell physiology Cells Cellular Morphology Choroid Communities Complex Computer software Data Diabetic Retinopathy Diagnostic Disease Eye Eye Banks Eye diseases Fright Future Gene Expression Gene Expression Profile Genes Genetic Genomics Geographic Locations Health Heterogeneity Hour Human Human Genetics Image Immunohistochemistry Laboratories Light Measures Methods Microglia Midbrain structure Mus Mutation Optic Nerve Pathologic Pattern Perception Phenotype Population Precision therapeutics Process Recovery Retina Retinal Diseases Role Sampling Signal Transduction Stains Structure Structure of retinal pigment epithelium Surface Testing Thalamic structure Thick Thinness Tissues Translations Vision Visualization cell type computerized tools deep learning denoising disability genome wide association study improved insight learning strategy macula medical specialties millimeter novel open source precision medicine protein expression single-cell RNA sequencing success therapeutic target transcriptome sequencing transcriptomics user-friendly web app web site

项目摘要

PROJECT SUMMARY Vision, the most important of the human senses, occupies 25% of the brain function. It requires an orchestrated coordination between all parts of the eye. Of all the parts, the retina is the most vital for normal perception of an image. It is a precisely layered structure lining the surface of the back of the eye, comprising many millions of cells packed together in a tightly knit network. The optic nerve connects the retina with the brain. The retina not only receives light, but also processes it, and transmits downstream signals to the midbrain and the thalamus. When the retina becomes diseased, the unfortunate result is blindness, which is the most feared disability. Diseases that affect the retina are complex because of the diverse number of cell types and total number of cells involved. It remains challenging to assess if pathological phenotypes affect diverse cell populations versus highly specific cell types. While advances in retinal disease diagnostics have progressed rapidly, treatments for retinal diseases directed at primary genetic defects have progressed slowly. Despite major successes in genetics, the vision community is lagging behind the advances in precision medicine occurring in other specialties. Modest progress is due in part to an incomplete understanding of human retinal biology. Anatomical differences between humans and commonly used animal models have severely hindered the translation of results from laboratory to human health. Therefore, there is an urgent need to collect and analyze retinal cells from human eyes to advance our understanding of human retinal diseases and assess the cell type conservation between mouse and human. Recent technologic breakthroughs in single-cell RNA-seq (scRNA-seq) have made it possible to measure gene expression in single cells, paving the way for exploring cellular heterogeneity. Collaborating with the Alabama Eye Bank, we will deeply sample human retinal cells, fully characterize cell diversity, and elucidate the functional roles of findings from genome- wide association studies for retinal diseases. We propose the following aims. Aim 1 will generate scRNA-seq data from eyes of 20 healthy adult human donors, and produce de-noised gene expression data for downstream analyses. Aim 2 will characterize cell diversity in human retina and supporting tissues, and validate novel cell type-specific marker genes by immunohistochemistry. Aim 3 will infer cell type compositions and allele-specific gene expression in each cell type by integrating scRNA-seq and bulk RNA-seq data from normal human eyes. These pioneering studies leverage novel methods and interdisciplinary expertise to characterize cell type-specific gene expression in human retina and supporting tissues. By detailed characterization of the cell atlases in four geographical areas in human eye, our study will provide novel insights into cell-type specific functions that can power precision therapeutic targeting of retinal diseases.

项目总结